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Pharmaceutical Chemistry Journal - published by
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GB-115 is an original peptide anxiolytic with the structure N-(6-phenylhexanoyl)glycyl-L-tryptophan amide that has been developed at Zakusov State Institute of Pharmacology (Moscow).
The physicochemical properties of GB-115 parent substance were studied. Analytical procedures for it were elaborated. General
pharmacopoeial quality characteristics have been determined. UV, IR, and NMR spectra have been measured. A method for determining
foreign impurities in GB-115 parent substance that is based on HPLC was developed.
Content Type Journal Article
Pages 1-4
DOI 10.1007/s11094-012-0695-2
Authors
V. S. Klumova, Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, 125315, Russia
L. N. Grushevskaya, Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, 125315, Russia
N. I. Avdyunina, Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, 125315, Russia
B. M. Pyatin, Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, 125315, Russia
M. S. Sergeeva, Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, 125315, Russia
L. M. Gaevaya, Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, 125315, Russia
M. E. Dudenkova, Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, 125315, Russia
Administration of thioctic acid in doses of 35 and 70 mg/kg into rats under conditions of chronic alcohol intoxication resulted
in the concentration of reduced glutathione and the activities of glutathione peroxidase, glutathione reductase, NADP-isocitrate
dehydrogenase, and glucose-6-phosphate dehydrogenase in rat heart approaching the control levels. The obtained data provided
deeper insight into the molecular mechanisms of thioctic acid action and a basis for further research aimed at expanding the
range of indications for use of thioctic acid.
Content Type Journal Article
Pages 1-3
DOI 10.1007/s11094-012-0685-4
Authors
T. N. Popova, Voronezh State University, Voronezh, Russia
H. Allekrad, Voronezh State University, Voronezh, Russia
T. I. Rakhmanova, Voronezh State University, Voronezh, Russia
A. V. Semenikhina, Voronezh State University, Voronezh, Russia
L. V. Matasova, Voronezh State University, Voronezh, Russia
Water-soluble polymeric esters of the antibiotic cefuroxime were synthesized for the first time by the carbodiimide method
using low-molecular-weight poly-(N-2-hydroxypropyl)methacrylamide as a carrier. The synthesized compounds contain 16.6 and 19.5 wt% antibiotic, exhibit antibacterial
activity with respect to S. aureus, and are subject to hydrolysis in physiological solution at 37°C (45.4 and 53.2% for 24 and 30 h, respectively).
Content Type Journal Article
Pages 1-4
DOI 10.1007/s11094-012-0687-2
Authors
M. V. Solovskii, Institute of Macromolecular Compounds, Russian Academy of Sciences, St. Petersburg, 199004 Russia
M. S. Borisenko, Institute of Macromolecular Compounds, Russian Academy of Sciences, St. Petersburg, 199004 Russia
M. Yu. Smirnova, Institute of Macromolecular Compounds, Russian Academy of Sciences, St. Petersburg, 199004 Russia
New pyrazoles; 1,2,4-triazoles; β- and γ-glycols; amidrazones; and amines of the adamantane series have been synthesized.
Their activity with respect to smallpox vaccine virus has been studied. High anti-smallpox activity was observed for ethyl-3-(1-adamantyl)-5-(4-methylphenyl)-1H-pyrazole-4-carboxylate (VI) and 1,4-bis(1-adamantyl)-1,4-butanediol (XII).
Content Type Journal Article
Category Search for New Drugs
Pages 1-5
DOI 10.1007/s11094-012-0686-3
Authors
I. K. Moiseev, Samara State Technical University, Samara, Russia
S. A. Kon’kov, Samara State Technical University, Samara, Russia
K. A. Ovchinnikov, Samara State Technical University, Samara, Russia
N. M. Kilyaeva, Samara State Technical University, Samara, Russia
K. M. Bormasheva, Samara State Technical University, Samara, Russia
O. N. Nechaeva, Samara State Technical University, Samara, Russia
M. V. Leonova, Samara State Technical University, Samara, Russia
Yu. N. Klimochkin, Samara State Technical University, Samara, Russia
S. M. Balakhnin, Vector State Research Center for Virology and Biotechnology, Koltsovo, Novosibirsk Oblast, Russia
N. I. Bormotov, Vector State Research Center for Virology and Biotechnology, Koltsovo, Novosibirsk Oblast, Russia
O. A. Serova, Vector State Research Center for Virology and Biotechnology, Koltsovo, Novosibirsk Oblast, Russia
E. F. Belanov, Vector State Research Center for Virology and Biotechnology, Koltsovo, Novosibirsk Oblast, Russia
3-Bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (BDB) is a bromophenol purified from the marine red alga Rhodomela confervoides and exhibits potent protein tyrosine phosphatase 1B (PTP1B) inhibition (IC50 = 1.7 µmol/L). In an effort to improve the PTP1B inhibitory activity, a series of derivatives were designed, synthesized, and evaluated in vitro. The preliminary structure–activity relationship indicated that the tricyclic scaffold and multi-bromine atoms (four to five) attached to the aryl rings are important for PTP1B inhibition. Among these, compound 26 exhibited remarkable inhibitory activity against PTP1B with an IC50 of 0.89 µmol/L, which was approximately two-fold more potent than the initial lead compound BDB.
A series of bromophenol derivatives were designed, synthesized, and evaluated as PTP1B inhibitors in vitro based on the lead compound BDB. Compound 26 (R1 = CH3, R2 = H, R3 = 2,3-Br, and R4 = 2,3-Br) exhibited remarkable inhibitory activity against PTP1B with an IC50 of 0.89 µmol/L, which was approximately two-fold more potent than BDB.
A series of novel compounds were synthesized in reactions of N3-substituted amidrazones with cis-1,2-cyclohexanedicarboxylic anhydride: linear, isoindole, and triazole derivatives. All new structures were confirmed by H1 NMR and IR spectrometry as well as elemental analysis. Potential biological effects of new compounds were predicted with the Prediction of Activity Spectra for Substances (PASS) program. Antiviral, antibacterial, analgesic, and anti-inflammatory activities were experimentally verified.
A series of novel compounds were synthesized in reactions of N3-substituted amidrazones with cis-1,2-cyclohexanedicarboxylic anhydride: linear, isoindole, and triazole derivatives. The potential biological effects of the new compounds were predicted with the PASS program. Antiviral, antibacterial, analgesic, and anti-inflammatory activities were verified experimentally.
A new class of biologically active 13-membered phosphorus-macroheterocycles (6a–l) were conveniently synthesized from 1,2-bis(salicylidene amino)-phenylene (1), by treating with phosporusoxychloride (3) and followed by reacting with various aromatic thiols and amines (5f–l) in one path, and in another path 1 was directly treated with various phosphorodichloridates (2a–e) in the presence of triethylamine at 0–10°C under N2 atmosphere in THF. All the title compounds were confirmed by analytical and spectral data (IR, 1H-, 13C-, 31P-NMR, and mass spectra) and screened for anti-oxidant activity. Among these compounds, 6k, 6e, and 6l containing nitro, fluoro, and chloro groups as substituents on the phenyl ring exhibited high anti-oxidant activity with effective inhibitory concentration (IC50) values.
A new class of anti-oxidatively active 13-membered phosphorus-macroheterocycles were conveniently synthesized and their activity was measured by DPPH radical scavenging, reducing power assay, and hydroxyl radical scavenging methods. The title compounds possess significant anti-oxidant activity.
Five new immunomodulators 1a–1e by using a trans-4-alkyl-substituted cyclohexane to replace the flexible C8 alkyl chain of Fingolimod were synthesized. For in-vitro test, the compounds were dissolved in DMSO as a stock solution and diluted to a desired concentration with RPMI 1640 nutrient solution. For in-vivo test, the compounds were prepared in pathogen-free saline containing 0.5% DMSO. These new immunomodulators displayed more potent immunoinhibitory activities in vitro and moderate immunomodulating activities in vivo. They show therapeutic effects on DNFB-induced DTH reaction and inhibitory effects on the antigen-specific T-cell proliferation.
Five new immunomodulators 1a–1e were synthesized by using a trans-4-alkyl-substituted cyclohexane to replace the flexible C8 alkyl chain of fingolimod. They show therapeutic effects on the DNFB-induced DTH reaction and inhibitory effects on antigen-specific T-cell proliferation.
Methylenebisphosponic acid tetraethyl ester (1) was added to 2-azido-7a–e and 2-chloroquinoline-3-chalcones 10a–e in boiling sodium ethanolate solution to give, via Michael addition, tetrazolo[1,5-a]quinoline-8a–d, 13a and 2-chloroquinoline-based bisphosphonates 11a–d, 14a in E-configuration. Further acid hydrolysis afforded the respective BP-acid analogues E-9a–d, 12a–d, 13b, and 14b in excellent yields. Anti-tumor activity screening for the new BP-acids at a dose of 10 µM utilizing 44 different human tumor cell lines representing breast, ovary, prostate, lung, and CNS cancer as well as leukemia and melanoma was carried out. Eight of ten tested compounds exhibited remarkable anti-tumor activity against breast and prostate cancer, and a promising anti-tumor sensitivity toward ovarian cancer and melanoma. Conversely, there was only scattered activity against leukemia and no noticeable action of these BP-acids on CNS or lung cancer. Based on the prediction results (PASS program), anti-inflammatory activity of the new acids was also determined in vivo, by the acute carrageenin induced paw edema in rats. Many of these compounds showed anti-inflammatory properties at a dose of 50 mg/kg body weight.
New bisphosphonates and bisphosphonic acids were synthesized and screened for anti-tumor activity. The results indicate that this moiety is an essential factor in developing the total pharmacological properties for the synthesized compounds whereas the type of the substituents attached to the quinoline nucleus determines and controls the potency.
In an attempt to find a new and a safer drug for tuberculosis, we have synthesized a series of fluoronitrobenzothiazolopyrazolines for antitubercular activity. The series comprises three subclasses: fluorobenzothiazolopyrazolines (11a–f), fluoronitrobenzothiazolopyrazoline, nitro group at 5th position (12a–f) and 4th position (13a–f). All compounds were screened for their in-vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain by using Middlebrook 7H-9 broth. An introduction of NO2 group at 5th position of benzothiazole ring (12a–f) increased the antitubercular activity whereas introduction of NO2 group at 4th position (13a–f) was found to decrease the activity remarkably. Two compounds from each series showing good antitubercular activity were tested for cytotoxicity on THP-1 cell lines and they showed low cytotoxicity.
Regioisomers of fluoronitrobenzothiazolo pyrazoline were synthesized and their activity on the Mycobacterium tuberculosis H37Rv strain was compared to the standard drugs streptomycin and pyrazinamide. The results revealed that the introduction of an NO2 group at the “5-position” of the benzothiazole ring (12a–f) increased the antitubercular activity.
In the present study, a new series of ethyl 2-(substituted benzylthio)-4-(3′-(ethoxycarbonyl)-biphenyl-4-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate derivatives was synthesized. The newly synthesized compounds were characterized by 1H-NMR, mass and C, H, N analyses. All newly synthesized compounds were screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes and Klebsiella pneumoniae) and antifungal (Aspergillus flavus, Aspergillus fumigatus, Candida albicans, Penicillium marneffei and Trichophyton mentagrophytes) activity. The results revealed that all synthesized compounds have a significant biological activity against the tested microorganisms. Compounds 8a, 8b, 8c, 8e, 8f, 8i, and 8j exhibited good antimicrobial activity.
Novel biphenylpyrimidines showing substituted benzylthio groups were synthesized and evaluated for their antibacterial and antifungal activity. All synthesized compounds have significant biological activity against the tested microorganisms. Compounds 8a, 8b, 8c, 8e, 8f, 8i, and 8j exhibited good antimicrobial activity.
Novel series of pyrazole derivatives were synthesized and tested for their in vivo anti-malarial activity using mice infected with chloroquine sensitive P. berghei at a dose level of 50 µmol/kg. The most active compounds were further tested in vitro against chloroquine resistant (RKL9) strain of P. falciparum. The in vivo anti-malarial activity study indicated that compounds 2a, 2b, 8a and 8b had mean percent suppression of 85%, 83%, 95% and 97%, respectively at equimolar dose level of the standard drug chloroquine diphosphate. Moreover, compounds 2a, 2b, 8a and 8b showed in vitro IC50 values lower (p < 0.05) than that of the standard drug chloroquine phosphate (0.188 ± 0.003 µM) using the RKL9 strain. Compound 8b was the most active with IC50 of 0.033 ± 0.014 µM. Generally, among the tested compounds, those containing a free carboxylic acid functional group on the pyrazole ring were the most active and this finding was supported by the docking results performed for the active compounds. The acute toxicity studies of the active compounds revealed that they have a good safety profile.
A novel series of pyrazole derivatives were synthesized and tested for their in vivo anti-malarial activity using mice infected with chloroquine sensitive P. berghei and P. falciparum. Compound 8b (R1 = Cl, R2 = COOH) was the most active with an IC50 of 0.0326 ± 0.014 µM. This finding was supported by the docking results performed for the active compounds. The acute toxicity studies of the active compounds revealed that they have a good safety profile.
Four series of compounds containing an anthraquinone-linked moiety and symmetrical or asymmetrical aminoacyl residues in side chains at positions 1,4-, 1,5-, 2,6-, and 2,7- were synthesized and evaluated for their inhibitory effects toward telomerase and hTERT expression. Of these, only compound B11 showed selective inhibition of telomerase activity. Although it is not as competent as several of the anthraquinones we identified previously, nevertheless, the result is consistent with that the general structure moiety at the 1,5-position of diaminoanthraquinone-linked compound is important for the telomerase inhibitory activity. Interestingly, compounds A6, A8, C8, and D8 exhibited selective repressing activities toward hTERT expression and showed less effect toward proliferation of the treated cancer cells. Although it is not apparent which structure moiety is responsible for the telomerase repression effects of these compounds, they could be further developed as potential anti-tumor agents.
This study shows how and to what extent the position of side chain substituents affects telomerase activity. Four series of compounds containing an anthraquinone-linked moiety and symmetrical or asymmetrical aminoacyl residues were synthesized and evaluated for their inhibitory effects towards telomerase and hTERT expression.
4,6-Dimethyl-1H-pyrazolo[3,4-b]pyridine-3-amine (1) was used as a key intermediate for the synthesis of imidazolopyrazole derivatives 7–11 upon interaction with 3-(2-bromoacetyl)-2H-chromen-2-one (2), 2-(benzothiazol-2-yl)-4-chloro-3-oxobutanenitrile (3), 2,3-dibromonaphthalene-1,4-dione (4), naphtha[2,3-b]oxirene-2,7-dione (5), 2,5-dichloro-3,6-dihydroxyhexa-2,5-diene-1,4-dione (6), respectively. Acetylation of 11 afforded the bis-acetyl 12. Also, the imidazolopyrimidine 15 was prepared via treatment of 1 with sodium 3,4-dioxo-3,4-dihydronaphthalene-1-sulfonate (13) in DMF followed by cyclization of the bis-pyrazolopyrimidine 14 with glacial acetic acid. On the other hand, compound 1 was reacted with (E)-1-(4-methoxyphenyl)-5-(piperidin-1-yl)pent-1-en-3-one hydrochloride (16), 2-hydroxy-3-((piperidin-1-yl)-methyl)-naphthalene-1,4-dione (17), 2-styryl-2H-indene-1,3-dione (18), enaminone 22, chloroquinoline-3-carbaldehyde 27a, chloroquinoline-(6-methyl)-3-carbaldehyde 27b and 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (28) to afford pyrazolo[3,4-a]pyrimidines 19–21, 23, 29a, 29b and 30, respectively. Also, the pyrazolopyrimidinone 33 was obtained via treatment of 1 with 1-cyanoacetyl-3,5-dimethylpyrazole (31) followed by cyclization of the formed intermediate 32 with glacial acetic acid. Finally, treatment of 1 with o-terephthalaldehyde in glacial acetic acid afforded diazepine 34. The newly synthesized compounds were screened for their antioxidant properties in which some of them exhibited promising activities. Compounds 1, 14, 15, 23, 26, 29a, 30 and 32 have the ability to protect DNA from the damage induced by bleomycin.
New synthesized pyrazolopyridine derivatives were screened for their antioxidant properties. Some of the tested compounds as 1, 14, 15, 23, 26, 29a, 30 and 32 have the ability to protect DNA from the damage induced by bleomycin.
A new series of benzo[6,7]cyclohepta[1,2-d]triazolo[4,3-a]pyrimidines 8a–l was synthesized via reaction of heterocyclic thione 4 or its methyl derivatives 10 with hydrazonoyl halides 5a–l. Also, reaction of compound 4 with a mixture of chloroacetic acid and aromatic aldehyde derivatives gave benzo[6,7]cyclohepta[1,2-d]thiazolo[3,2-a]pyrimidin-3-ones 12–14. The microanalyses and spectral data of the synthesized compounds are in full agreement with their molecular structure. All the newly synthesized products were screened against 5α-reductase and showed activities with good ED50 for all compounds.
A new series of benzo[6,7]cyclohepta[1,2-d]triazolo[4,3-a]pyrimidines 8a–l was synthesized via reaction of heterocyclic thione 4 or its methyl derivatives 10 with hydrazonoyl halides 5a–l. Also, reaction of compound 4 with a mixture of chloroacetic acid and aromatic aldehyde derivatives gave benzo[6,7]cyclohepta[1,2-d]thiazolo[3,2-a]pyrimidin-3-ones 12–14. All the newly synthesized products were screened against 5α-reductase and showed activities with good ED50 for all compounds.
In the present study, some amide derivatives were synthesized and their potential anticholinesterase properties were investigated. N-(Benzothiazol-2-yl)-2-[(5-amino/methyl-1,3,4-thiadiazol-2-yl)thio]acetamide derivatives were obtained by nucleophilic substitution of 2-chloro-N-(benzothiazole-2-yl)acetamide derivatives with appropriate 1,3,4-thiadiazole-2-thioles. The chemical structures of the compounds were elucidated by 1H-NMR, 13C-NMR and FAB+-MS spectral data and elemental analyses. Each amide derivative was evaluated for its ability to inhibit AChE and BuChE using a modification of Ellman's spectrophotometric method. The compounds were also investigated for their cytotoxic properties using MTT assay. 2-(5-Amino-1,3,4-thiadiazol-2-yl)thio-N-(benzothiazol-2-yl)acetamide derivatives have anticholinesterase activity, whereas 2-(5-methyl-1,3,4-thiadiazol-2-yl)thio-N-(benzothiazol-2-yl)acetamide derivatives have no inhibitory effect on enzyme activity. Among these compounds, it is clear that compound IIh is the most potent derivative.
Among these new compounds, compound IIh is the most potent inhibitor of AChE and BuChE with an IC50 value of 66 ± 0.71µg/mL and 48.75 ± 2.48 µg/mL, respectively.
A new series of 4-aryl-4H-chromenes bearing a 5-arylisoxazol-3-yl moiety at the C-4 position were prepared as potential anticancer agents. The in vitro cytotoxic activity of the synthesized compounds was investigated against a panel of tumor cell lines including MCF-7 (breast cancer), KB (nasopharyngeal epidermoid carcinoma), Hep-G2 (liver carcinoma), MDA-MB-231 (breast cancer), and SKNMC (human neuroblastoma) using the MTT colorimetric assay. Doxorubicin, a well-known anticancer drug, was used as positive standard drug. Among the synthesized compounds, the 5-(3-methylphenyl)isoxazol-3-yl analog (7j) showed the most potent cytotoxic activity against all five human tumor cell lines.
A series of 2-amino-3-cyano-4-(5-arylisoxazol-3-yl)-4H-chromenes were prepared and evaluated against five cancer cell lines including MCF-7 (breast cancer), KB (nasopharyngeal epidermoid carcinoma), Hep-G2 (liver carcinoma), MDA-MB-231(breast cancer), and SKNMC (human neuroblastoma). Compound 7j having 5-(3-methylphenyl)isoxazol-3-yl at the C-4 position was the most active compound.
In order to increase the intestinal permeability of valsartan, 14 esters and peptide derivatives of valsartan were chemically synthesized and their absorption characteristics were described. All derivatives were stable and could be better absorbed into the small intestine than valsartan. There are two barriers for the absorption of valsartan derivatives. The elongated half-life (t1/2) and stable blood concentrations for compound 4 due to the hydrolysis of the ester group in the second barrier were demonstrated in pharmacokinetic experiments. Furthermore, compound 4 also displayed modest anti-hypertension activity in vivo, which makes structural modification of valsartan, especially for the purpose of improvement of its intestinal permeability, valuable for further studies.
Fourteen valsartan peptide derivatives (VPDs) were synthesized and evaluated for their intestinal permeability. The mechanism of absorption and the pharmacokinetic and pharmacodynamic profiles for certain VPDs are also reported.
A new series of 3-hydroxy-8-nitroimidazo[5,1-b]-1,4,5,6-tetrahydropyrimidine systems, being potential tuberculostatic agents, were synthesized. These products are close structural analogs of the basic structure of the known antitubercular bicyclic nitroimidazooxazine PA-824. The structures of the products obtained were confirmed by X-ray methods on the example of 3-hydroxy-8-nitro-1-phenylaminoimidazo[5,1-b]-1,4,5,6-tetrahydropyrimidine. Evaluation of these products for their anti-tuberculosis effects revealed interesting structure–activity relationships.
A new series of 3-hydroxy-8-nitroimidazo[5,1-b]-1,4,5,6-tetrahydropyrimidine systems were synthesized. These products are close structural analogs of the basic structure of the antitubercular bicyclic nitroimidazooxazine PA-824. Evaluation of these compounds for their anti-tuberculosis effects revealed interesting structure–activity relationships.
A new series of N-(benzoylphenyl) and N-(acetylphenyl)-1-benzofuran-2-carboxamides (3a–3d and 4a′–4c′) were synthesized. Compounds (3a, 3b, and 4a′–4c′) were tested in vivo using Triton-WR-1339-induced hyperlipidemic rats as an experimental model for their hypolipidemic activity. The tested animals were divided into eight groups: control, hyperlipidemic, 3a, 3b, 4a′, 4b′, 4c′, and bezafibrate. At a dose of 15 mg/kg, the elevated plasma triglyceride (TG) levels were significantly reduced in compounds 3b (p <0.0001) and 4c′ (p <0.05) after 12 and 24 h compared to the normal control group. Furthermore, high-density lipoprotein-cholesterol levels were remarkably increased in compounds 3b (p <0.001) and 4c′ (p <0.05). Meanwhile, compound 4b′ slightly reduced the TG levels after 12 and 24 h. The present study demonstrated new properties of the novel series of benzofuran-2-carboxamides 3b and 4c′ as potent lipid-lowering agents. It is, therefore, reasonable to assume that compounds 3b and 4c′ may have a promising potential in the treatment of hyperlipidemia and coronary heart diseases.
A new series of N-(benzoylphenyl) and N-(acetylphenyl)-1-benzofuran-2-carboxamides (3a–3d and 4a′–4c′) were synthesized and most of them were tested in vivo for their hypolipidemic activity. Compounds 3b and 4c′ turned out to be potent lipid-lowering agents and thus may have a promising potential in the treatment of hyperlipidemia and coronary heart diseases.
The synthesis and the antitumor activity and fluorescent properties screening of novel bisphosphonate conjugates with cytotoxic 3,5-bis((hetero)arylidene)-4-piperidone residues were performed. The facile and rapid synthetic route was based on the aza-Michael addition of NH-3,5-bis((hetero)arylidene)-4-piperidones to tetraethyl ethylidenebisphosphonate. The synthesized compounds displayed high inhibitory properties towards Caov3, A549, PC3, and KB 3-1 human carcinoma cell lines. Among those, compounds bearing 4-cyano-phenyl and 3-pyridinyl substituents were revealed as the most active drug candidates with IC50 values in the range of 0.5–2.5 µM. Methylenebisphosphonate with 4-Me2N-C6H4 groups in the piperidone framework possessing fluorescence properties may be of interest for visualization of BPs skeletal distribution and cellular uptake in bones and other tissues.
Hybrid compounds were synthesized by linking the structural unit of cytotoxic 3,5-bis((hetero)arylidene)-4-piperidones with a bisphosphonate residue, and their in vitro antitumor activities and fluorescence properties were examined.
A new series of 2,5-diaryliminothiazolidin-4-ones were designed and synthesized as potent antiproliferative agents. The antiproliferative activities of the 25 target compounds were evaluated against three cancer cell lines (A549, H460 and HT29) by MTT assay. Pharmacological data indicated that most of the compounds possessed moderate activity, some showed remarkable activity against one or more cell lines. As the most promising compound, 8s (with IC50 values of 1.1, 0.01 and 1.3 µM against the A549, H460 and HT29 cell lines) was 1.1- to 270-fold more potent than the reference drug sorafenib. Furthermore, preliminary structure–activity relationships (SARs) were summarized to provide guidance for further design and discovery of 2-iminothiazolidin-4-one-based antiproliferative agents.
A new series of 2,5-diaryliminothiazolidin-4-ones were designed and synthesized as potent antiproliferative agents. The antiproliferative activities of the 25 target compounds were evaluated against three cancer cell lines (A549, H460 and HT29) by MTT assay. The most promising compound, 8s, was 1.1–270-fold more potent than the reference drug sorafenib. Preliminary structure–activity relationship data provide guidance for further design and discovery of 2-iminothiazolidin-4-one-based antiproliferative agents.
2-Tosylacetonitrile (1) when reacted with α,β-unsaturated nitriles 2a–c or a mixture of formaldehyde and 3-amino-2-substituted-pent-2-endinitriles 6a,b yielded pyridine derivatives 3a–c and 9a,b, respectively, while when subjected to react with salicylaldehyde yielded chromene derivatives 4 and 5, subsequently. The behavior of thiocarbamoyl derivative 10 derived from 1 towards some α-halogenated compounds have been investigated as well as its behavior towards elemental sulfur and phenyl isothiocyanate. Newly synthesized compounds were screened for their antioxidant activity, erythrocytes haemolysis and bleomycin-independent DNA damage. Some of the tested compounds exhibited promising activities.
2-Tosylacetonitrile (1) was reacted to pyridine derivatives (3a–c, 9a,b) or chromene derivatives (4, 5). The behavior of the thiocarbamoyl derivative 10 derived from 1 towards some α-halogenated compounds was investigated as well as its behavior towards elemental sulfur and phenyl isothiocyanate. The newly synthesized compounds were screened for their antioxidant, erythrocyte hemolysis and bleomycin-independent DNA damage activities.
The interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in the pathogenesis of various inflammatory and autoimmune diseases. Small molecules that block these interactions have been targeted as potential therapeutic agents against acute and chronic inflammatory diseases. In an effort to identify potent intercellular cell adhesion molecule-1 (ICAM-1) inhibitors, a large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones and their analogs (54 in total) have been synthesized and screened for their ICAM-1 inhibitory activity. The structure-activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated the possible mechanism for their ICAM-1 inhibitory activities. The most active compound was found to be 79.
A large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones as well as their analogs (54 in total) were synthesized and screened for their ICAM-1 inhibitory activity. The structure-activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated a possible mechanism of their ICAM-1 inhibitory activities. The most active compound was found to be 79.
A new series of N,N′-(benzene-1,3-diyldi-1,3,4-oxadiazole-5,2-diyl)bis{2-[(5-benzene-1,3-diyl-1,3,4-oxadiazol-2-yl)amino]acetamide}(macrocycle 1), N,N′-(benzene-1,3-diyldi-1,3,4-thiadiazole-5,2-diyl)bis{2-[(5-benzene-1,3-diyl-1,3,4-thiadiazol-2-yl)amino]acetamide} (macrocycle 2) and S,S′-[benzene-1,3-diylbis(4H-1,2,4-triazole-5,3-diyl)]bis{[(5-benzene-1,3-diyl-4H-1,2,4-triazol-3-yl)sulfanyl]ethanethioate}(macrocycle 3) was synthesized from isophthalic dihydrazide (4) through a multistep reaction sequence. All the synthesized compounds were screened for their inhibitory effect against four different bacterial strains: P. aeruginosa ATCC-20852, K. pneumoniae MTCC-618, S. aureus ATCC- 29737, S. typhi MTCC- 3214. The synthesized compounds showed a significant zone of inhibition and the results were comparable with that of the standard drug ciprofloxacin. The synthesized compounds were further studied for their possible in vitro antioxidant effects by DPPH scavenging, total antioxidant capacity, total reductive capacity and H2O2 scavenging activity. The results indicated that the in vitro antioxidant activity for all the three molecules was efficient when compared to the standards. The DNA interaction behavior of macrocycles 1–3 with CT-DNA was investigated by the absorption spectra obtained (Kb constant for 1 is 4.53 × 104 M−1, for 2 is 5.75 × 104 M−1 and for 3 is 5.86 × 104 M−1). Based on the results it can be interpreted that the reducing power effect of the newly synthesized compounds demonstrates a direct effect on DNA binding and hence inhibiting the bacterial growth through their action on DNA by inhibiting DNA replication or DNA transcription.
A new strategy is demonstrated to introduce oxadiazole, thiadiazole or triazole rings into macrocycles employing novel precursors, without using high dilution conditions. The synthesized compounds were screened for their inhibitory effects against four different bacterial strains.
(3,4-Dihydroxyphenyl)(2,3,4-trihydroxyphenyl)methanone (5) and its two derivatives with bromine were synthesized from reactions such as bromination and demethylation of (3,4-dimethoxyphenyl)(2,3,4-trimethoxyphenyl)methanone (6). The Wolf-Kishner reduction product (9) of 6 and its three derivatives with bromine were obtained. 4-(3,4-Dihydroxybenzyl)benzene-1,2,3-triol and its dibromide derivative (16) were also synthesized from 9 and the corresponding dibromide derivative. The in vitro antioxidant activities of nine new compounds synthesized in these reactions were determined by analyzing the radical scavenging activities of bromophenols for 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), 1,1-diphenyl-2-picryl-hydrazyl (DPPH), N,N-dimethyl-p-phenylenediamine (DMPD), and the superoxide anion radical () and examining the total reducing power through Fe3+-Fe2+ transformation, FRAP and CUPRAC assays and the ferrous ions (Fe2+) chelating activities. Moreover, the results of these activities were compared to those of standard antioxidant compounds such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol, and trolox. The results showed that the synthesized bromophenols had effective antioxidant power. The phenol 5 with two phenolic rings and five phenolic hydroxyl groups was the most potent antioxidant and radical scavenger. In conclusion, the new compounds are promising molecules to be used owing to their potential antioxidant properties.
(3,4-Dihydroxyphenyl)(2,3,4-trihydroxyphenyl)methanone (5) and its two derivatives with bromine were synthesized. 4-(3,4-Dihydroxybenzyl)benzene-1,2,3-triol and its dibromide derivative (16) were also synthesized. The in vitro antioxidant activities of nine new compounds were determined, showing that the synthesized bromophenols had effective antioxidant power. The phenol 5 with two phenolic rings and five phenolic hydroxyl groups was the most potent antioxidant and radical scavenger.
As part of our studies focused on the design and synthesis of new antimicrobial agents a series of 7-fluoro-3,4-dihydro-2H-1,4-benzothiazine derivatives (4a–4f, 4h) and 7-fluoro-2H-1,4-benzothiazin-3(4H)-one analogues (4j–4o) were synthesized and evaluated for their in vitro inhibitory activity against a representative panel of Gram-positive and Gram-negative bacteria strains and also toward selected fungi species. These compounds were prepared in one step from chloro-substituted-2-amino-5-fluorobenzenethiol 6a–6c. The biological screening identified in compounds 4a, 4j and 4l the most promising results of both series showing an interesting antimicrobial activity. Our antibiotic investigation was also completed by testing the key intermediates 6a–6c. Surprisingly, 6a–6c emerged as the compounds exhibiting the highest antimicrobial activity by possessing a remarkable antibacterial effect against the Gram-positive strains with MIC (minimal inhibitory concentration) values between 2 and 8 µg/mL and the fungi panel with MIC values between 2 and 8 µg/mL. These results may prove useful in the design of a novel pool of antimicrobial agents.
Benzothiazine, benzothiazinones and amino-5-fluorobenzenethiol derivatives were prepared to identify compounds with a potent antimicrobial profile. All obtained compounds were screened for in vitro antibacterial activity against Gram-positive and Gram-negative bacteria strains and a fungi panel. The most active compounds, substituted-2-amino-5-fluorobenzenethiol, exhibited an interesting antibacterial activity with MIC values between 2 and 8 µg/mL against both Gram-positive bacteria and the fungi panel.
The synthesis of a series of novel α-aminosubstituted phosphonates was accomplished by the reaction of various substituted aldehydes with an amine amlodipine (3-ethyl 5-methyl (±)2-((2-aminoethoxy)methyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridene-3,5-dicarboxylate) followed by diethylphosphite/dibutylphosphite in ethanol using SnCl2.2H2O as a Lewis acid catalyst, under conventional and ultrasonic irradiation. Their structures were established by analytical and spectral data. The title compounds showed good antibacterial, antifungal and antiviral activity depending on the nature of the bioactive groups at the α-carbon.
A new class of α-aminosubstituted phosphonates was synthesized and evaluated for their antimicrobial and antiviral activity.
A new series of pyrano[4,3-b]pyran 4a–i and pyrano[3,2-c]chromene 6a–r derivatives bearing a 2-thiophenoxyquinoline nucleus were synthesized by reaction of 2-(4-(un)-substituted thiophenoxy)quinoline-3-carbaldehydes 2a–i with 6-methyl-4-hydroxypyran-2-one 3 and 4-hydroxy-6-(un)-substituted-2H-chromen-2-one 5a–b respectively and malononitrile at room temperature in the presence of KOH as a basic catalyst. All the compounds were screened against three Gram-positive bacteria (Streptococcus pneumoniae, Bacillus subtilis, Clostridium tetani), three Gram-negative bacteria (Salmonella typhi, Escherichia coli, Vibrio cholerae) and two fungi (Candida albicans, Aspergillus fumigatus) using the broth microdilution MIC (minimum inhibitory concentration) method. Upon antimicrobial screening, it was observed that the majority of the compounds were found to be active against Bacillus subtilis, Clostridium tetani and Candida albicans as compared to standard drugs.
A new series of pyrano[4,3-b]pyran 4a–i and pyrano[3,2-c]chromene 6a–r derivatives bearing a 2-thiophenoxyquinoline nucleus were synthesized. All compounds were screened against three Gram-positive bacteria, three Gram-negative bacteria and two fungi. The majority of the compounds were found to be active against Bacillus subtilis, Clostridium tetani and Candida albicans as compared to standard drugs.
Three series of novel 1,3,5-trisubstituted 2-pyrazoline derivatives containing thiophene and benzodioxol moieties as potential antitumor agents were synthesized. The in vitro antitumor activity of the obtained compounds was determined at the National Cancer Institute (NCI). The 5-(benzo[d][1,3]dioxol-5-yl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (9a) is the most prominent of the compounds due to its remarkable activity toward leukemia (RPMI-8226), renal cancer (UO-31) and prostate cancer (DU-145) cell lines with GI50 values of 1.88, 1.91 and 1.94 µM, respectively.
Three series of novel 1,3,5-trisubstituted 2-pyrazoline derivatives containing thiophene and benzodioxol moieties as potential antitumor agents were synthesized. 5-(Benzo[d][1,3]dioxol-5-yl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (9a) shows remarkable activity toward leukemia, renal cancer and prostate cancer cell lines with GI50 values of 1.88, 1.91 and 1.94 µM, respectively.
Two divergent series of novel chalcone analogs, one derived from 1-cyclohexylpyrrolidin-2-one and the other derived from 1-benzo[f]chromanone, were designed, synthesized and evaluated for cytotoxicity against two murine cancer cell lines. Two 1-benzo[f]chromanone analogs, 4g and 4j yielded moderate toxicity against both melanoma B16 and lymphoma L1210 cell lines with IC50 values between the range of 5 and 6 µM. With an IC50 value of 3.4 µM, compound 4g was also active against human MDA-MB-435 melanoma cells. X-ray structures of the β-hydroxy ketone product (4a) and the α,β-unsaturated ketone (4h) were collected, and confirm the syn-configuration between the carbonyl moiety and the β-vinylic proton in 4h. X-ray structures of two 1-cyclohexylpyrrolidin-2-one derivatives were also obtained, and both showed an E-configuration for the double bond.
Twenty-four chalcone analogs and one aldol product derived from 1-benzo[f]chromanone and N-cyclohexylpyrrolidinone were synthesized and tested for cytotoxicity against murine cancer cells B16 and L1210. One 1-benzo[f]chromanone derivative (4g), containing a 3,4,5-trimethoxy benzylidene moiety, was quite active also against human MDA-MB-435 melanoma cells. The structure and conformation of the target compounds were ascertained by single crystal X-ray analysis of four compounds.
A new group of regioisomeric 2,3-diaryl-1,3-benzdiazinan-4-ones, possessing a methyl sulfonyl pharmacophore, were synthesized and their biological activities were tested for cyclooxygenase-2 (COX-2) inhibitory activity. In vitro COX-1/COX-2 inhibition studies identified 3-(p-fluorophenyl)-2-(4-methylsulfonylphenyl)-1,3-benzdiazinane-4-one (2b) as a potent and highly selective (IC50 = 0.07 µM; selectivity index = 572.8) COX-2 inhibitor.
A new group of regioisomeric 2,3-diaryl-1,3-benzdiazinan-4-ones, possessing a methyl sulfonyl pharmacophore, were synthesized and their biological activities were tested for cyclooxygenase-2 (COX-2) inhibitory activity. In vitro COX-1/COX-2 inhibition studies identified 3-(p-fluorophenyl)-2-(4-methylsulfonylphenyl)-1,3-benzdiazinane-4-one (2b) as a potent and highly selective (IC50 = 0.07 µM; selectivity index = 572.8) COX-2 inhibitor.
The versatile synthon (E)-2-((dimethyl amino)methylene)cyclooctanone (2) was used as a key intermediate for the synthesis of cyclooctanones and cyclooctane-based heterocycles with pyrazole, isoxazole, pyrimidine, pyrazolopyrimidine, triazolopyrimidine and imidazopyrimidine derivatives via its reactions with several nitrogen nucleophiles. The newly synthesized compounds were screened in vitro for their antimicrobial activity against pathogenic microorganisms (Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans). Most of the tested compounds showed moderate to high antibacterial and antifungal effects against the tested pathogenic microorganisms. Among the synthesized compounds, 2-((p-sulfonamidophenyl)methylene)cyclooctanone (5) showed excellent activity against Listeria monocytogenes.
The synthon (E)-2-((dimethyl amino)methylene)cyclooctanone (2) was used as key intermediate for the synthesis of cyclooctanones and cyclooctane-based heterocycles. The newly synthesized compounds were screened in vitro for their antimicrobial activity against pathogenic microorganisms.
A series of 1-(4-methoxyphenyl)-2-[5-{(biphenyl-4-yloxy)methyl}4-(substituted phenyl)-3-mercapto-(4H)-1,2,4-triazol-3-ylthio)] ethanones (6a–6s) and 4-(substituted phenyl)-3-(morpholin/pyrrolidin-4-ylmethylthio)-5-(4-phenylphenoxymethyl)-4H-1,2,4-triazoles (7a–7e) were synthesized in order to obtain new compounds with potent anti-inflammatory and analgesic activity with insignificant ulceration. Among the synthesized compounds, (6c), (6e), (6g) and (6l) from triazole series and (7b) and (7e) from Mannich base series were found to exhibit significant anti-inflammatory activity with 59.69, 59.69, 64.69, 79.84, 54.54, 79.69% and 52.55, 57.50, 72.52, 83.03, 60.06, 84.08% inhibition of paw edema at 3 h and 5 h respectively, in comparison to the standard drug ibuprofen (78.93 and 82.58% at 3 h and 5 h). The active compounds were further tested for their analgesic activity and gastric ulceration study. Compounds 6g, 7b and 7e exhibited significant analgesic activity with reaction time (3.60, 3.22, 3.88 s) respectively at 60 min. without causing any gastric irritation. These compounds were also screened for their in vitro antimicrobial activity, Compounds 6f, 6g, 6h, 6l, 6o, 6p, 7a, 7b and 7c showed significant zone of inhibition against various antimicrobial stains. It is concluded that the compounds 6g, 7b and 7e possess a good spectrum of activities. Compound 7e may be considered potent for development of better anti-inflammatory agent. The antimicrobial activity revealed that most of the compounds showed moderate to significant activity. Compounds containing nitro, chloro, bromo and fluoro group showing better activity. All the compounds from 7a, 7b and 7e were active against gram positive bacteria (S. aureus).
A series of 1-(4-methoxyphenyl)-2-[5-{(biphenyl-4-yloxy)methyl}4-(substituted phenyl)-3-mercapto-(4H)-1,2,4-triazol-3-ylthio)] ethanones and 4-(substituted phenyl)-3-(morpholin/pyrrolidin-4-ylmethylthio)-5-(4-phenylphenoxymethyl)-4H-1,2,4-triazoles were synthesized to obtain new compounds with potent anti-inflammatory and analgesic activity but low ulceration capacity.
A mild and versatile method for the synthesis of some novel indole-1-carbinols has been developed via one-pot reaction of indoles and paraformaldehyde in the presence of an excess of CaO, MgO, ZnO or TiO2. The solvent-free reaction provided all the indole derivatives in moderate to good yields and short reaction times. Moreover, the effect of some selected indole-1-carbinols on cell proliferation of the hepatoma cell line FaO was evaluated.
In the present work, we propose a simple and solvent-free protocol for the synthesis of novel indole-1-carbinols also studying their stability in acidic milieus. Some selected compounds showed an interesting apoptotic effect on FaO cells.
In an attempt to find a new class of antimicrobial agents, a series of benzothiazoles, 1,3-thiazolo[5,4-b]pyridines, 4H-3,1-benzothiazines, naphtho[2,3-d][1,3]thiazole-4,9-diones and other related compounds containing a 2,4-dihydroxyphenyl moiety were prepared. They were obtained via the reaction of aryl-modified sulfinyl[bis(2,4-dihydroxyphenylmethanethione)]s with appropriate commercial chemical reagents in the endocyclization processes. The MIC values of the compounds towards eight reference bacterial strains were assessed by the two-fold serial micro-dilution broth method. They exhibited inhibitory effects against the Gram-positive strains tested opposite to Gram-negative ones. Some compounds were more effective than the reference drug. 4-(6-Chloro-4H-3,1-benzothiazin-2-yl)-6-methylbenzene-1,3-diol (5b) due to its very good activity (MIC from 1.56 to 3.13 µg/mL) and low cytotoxicity (IC50 > 50 µg/mL) may be regarded as a promising precursor for the development of novel antibacterial agents.
A series of benzothiazoles, 1,3-thiazolo[5,4-b]pyridines, 4H-3,1-benzothiazines, naphtho[2,3-d][1,3]thiazole-4,9-diones and other related compounds containing a 2,4-dihydroxyphenyl moiety were prepared and their MIC values towards eight reference bacterial strains were determined. 4-(6-Chloro-4H-3,1-benzothiazin-2-yl)-6-methylbenzene-1,3-diol may be regarded as a promising precursor for the development of novel antibacterial agents.
Structural feature analysis of chlorogenic acid derivatives made up of varying lengths of alkyl groups as α-glucosidases inhibitors were performed by QSAR techniques. The statistically significant models derived from the study were validated by leave one out, Y-randomization and test set methods. The predictive capacity of the models was assessed by its validation parameters such as crossvalidated correlation coefficients (Q2), predictive residual analysis and other correlation parameters. The results obtained from the study show that the models were constructed with vsurf like properties (vsurf_ID4, vsurf_ID7 and vsurf_CW8), partial charge (Q_VSA_FNEG) and conformation dependent charged (dipoleX) descriptors. The integy moments of hydrophobicity descriptors (ID4 and ID7) are contributed for the inhibitory activity of the α-glucosidases enzymes of both the species. The vsurf_ID7 descriptor has contributed significantly (negatively) for the inhibitory activity prediction of α-glucosidases enzymes of S. cerevisiae. The partial negative charge on the surface of the molecules is detrimental for the activity, which reveals that the active site of the enzymes may have negatively charged groups. The pharmacophore analysis results also confirm the presence of hydrophilic properties on the vdW surface of the molecules. These results explain that the active sites of α-glucosidase enzymes of both the species have the same environment for the interaction. The alkyl side chain on the molecules is important for the pharmacokinetic behavior of the molecules and reduces the interaction energy of the molecules with the water. Hence, these results will be useful for designing novel molecules with multiple activities.
Structural feature analyses of chlorogenic acid derivatives with alkyl groups of varying lengths as α-glucosidase inhibitors were performed by QSAR techniques. The statistically significant models derived from the study were validated by leave-one-out, Y-randomization and test set methods. The predictive capacity of the models was assessed by their validation parameters, such as cross-validated correlation coefficients (Q2) and predictive residual analysis.
A new series of 1,4-disubstituted phthalazinylpiperazine derivatives 7a–f, 12a–f and 20a–f were designed and synthesized in order to develop potent and selective antitumor agents. The target compounds were screened for their cytotoxic activities against A549, HT-29 and MDA-MB-231 cancer cell lines in vitro. Among them, compounds 7a–f exhibited excellent selectivity for MDA-MB-231 with IC50 values ranging from 0.013 µM to 0.079 µM. The most promising compound, 7e (IC50 = 2.19 µM, 2.19 µM, 0.013 µM), was 9.3, 10, and 4.9 × 103 times more active than vatalanib (IC50 = 20.27 µM, 21.96 µM, 63.90 µM), respectively.
A new series of 1,4-disubstituted phthalazinylpiperazine derivatives 7a–f, 12a–f and 20a–f were designed and synthesized, and their cytotoxic activities against A549, HT-29 and MDA-MB-231 cancer cell lines in vitro were compared to that of vatalanib.
Various 1-[6-(4-substituted phenyl)-3-cyano-4-(substituted phenyl)-pyridin-2-yl]-5-oxopyrrolidine-3-carboxylic acids (3a–t) were designed and synthesized by clubbing pyrrolidinones and pyridines, the two active anticonvulsant pharmacophores. All the synthesized compounds fulfilled the requirements of suggested pharmacophoric model for anticonvulsant activity. Their in vivo anticonvulsant evaluation was performed by maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) tests. The minimal motor impairment was assessed by rotorod test and the estimation of various liver enzymes was performed to check the magnitude of liver toxicity posed by the synthesized compounds. Compounds 3d and 3k displayed comparable anticonvulsant activity to the standard drugs with ED50 values of 13.4 and 18.6 mg/kg in electroshock screen, repectively. The compounds 3d and 3k were also found to have encouraging anticonvulsant activity (ED50 = 86.1 and 271.6 mg/kg, respectively) in scPTZ screen. Interestingly, they did not show any sign of motor impairment at the maximum dose administered and were not toxic to the liver.
1-[6-(4-Substituted phenyl)-3-cyano-4-(substituted phenyl)-pyridin-2-yl]-5-oxopyrrolidine-3-carboxylic acids (3a–t) were designed and synthesized by clubbing two active anticonvulsant pharmacophores, pyrrolidinone and pyridine. Their in vivo anticonvulsant evaluation was performed by maximal electroshock seizure and subcutaneous pentylenetetrazole tests. Compounds 3d and 3k displayed comparable anticonvulsant activity to the standard drugs with ED50 values 13.4 and 18.6 mg/kg in electroshock screen repectively. Such promising compounds may act as lead molecules for future investigations.
Arglabin derivatives varied at the endo- or exo-cyclic double bond were synthesized and studied in a colorimetric sulforhodamine B assay for their cytotoxicity. Variations on the endocyclic double bond led to compounds of reduced cytotoxicity whereas derivatives from the reaction of the α-methylene-γ-butyrolactone moiety led to compounds of similar or only slightly reduced cytotoxicity but different, cell line-dependent selectivity. In addition, arglabin is an excellent starting material for the synthesis of the guaianolide arborescin.
Arglabin derivatives varying at the endo- or exo-cyclic double bond were synthesized. Variations on the endocyclic double bond led to compounds of reduced cytotoxicity whereas derivatives from the reaction of the α-methylene-γ-butyrolactone moiety led to compounds of similar or slightly reduced cytotoxicity but different, cell line-dependent selectivity.
The extracts of the roots of licorice have been used in traditional and folk medicine to treat a broad variety of maladies. The main ingredient of these extracts is glycyrrhicinic acid. Its aglycon, glycyrrhetinic acid, has many biological activities, among them a pronounced cytotoxicity against tumor cells. In this study we varied glycyrrhetinic acid at position C-30 to get “simple” derivatives, for example esters, amides and a nitrile. The influence of these changes on the cytotoxic activity is noteworthy and was determined by a colorimetric sulphorhodamine B test using 7 human tumor cell lines and mouse embryonic fibroblasts (NIH3T3) for comparison. A Trypan blue test as well as an acridine orange/ethidium bromide test was used to discover the ability of the compounds to induce apoptosis.
Some esters of glycyrrhetinic acid show improved antitumor activity; they act by apoptosis.
A series of novel 7-alkoxyl substituted indolizinoquinoline-5,12-dione derivatives were synthesized. The cholinesterase inhibition assays indicated that most synthesized compounds exhibited good activity for acetylcholinesterase (AChE) and high selectivity index of AChE over butyrylcholinesterase (BuChE). Compound 12b exhibited the most potent AChE inhibitory activity with an IC50 value of 0.068 µM and the highest selectivity index of 144. Kinetic study of AChE indicated that a mixed type of inhibition pattern existed for these indolizinoquinoline-5,12-dione derivatives. Molecular docking study indicated that compound 12b could bind to both the catalytically active site and the peripheral anionic site of AChE.
A series of novel 7-alkoxyl substituted indolizinoquinoline-5,12-dione derivatives were synthesized. The cholinesterase inhibition assays indicated that compound 12b exhibited the most potent AChE inhibitory activity and the highest selectivity index.
Substituted s-triazine derivatives are believed to exert their antibacterial effects by nonspecific mechanisms. We have assessed
the extent to which physicochemical properties can be used to promote discriminative activity of these compounds. In the search
for new and efficient antibacterial agents, a series of substituted phenylthiazolyl s-triazines were synthesized and screened
for their in vitro antibacterial activity against three Gram positive (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus) and three Gram-negative (Salmonella typhi, Escherichia coli, Klebsiella aerogenes) bacterial species by the broth dilution technique as recommended by European Committee for antimicrobial susceptibility
testing (EUCAST) with reference to streptomycin.
Content Type Journal Article
Pages 1-5
DOI 10.1007/s11094-011-0607-x
Authors
P. Gahtori, Dev Sthali College of Pharmacy, Lalpur Rudrapur, 263148 India
A. Das, Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, 786004 India
R. Mishra, Division of Pharmacology and Toxicology, Central Drug Research Institute, Lucknow, 226001 India
Assay of amoxicillin in capsules performed in accordance with the US Pharmacopeia by liquid chromatography was compared with
a method based on mercurimetric titration, developed by ourselves, in which the internal indicator was an azo derivative of
theophylline, i.e., benzenesulfonamide, N-(2,6-dimethoxy-4-pyrimidinyl)-4-[(4-methylamino-5-methylcarbamoyl)]azo2. The analysis results showed that mercurimetric assay was specific and easily performed in laboratory conditions and can
be used as an alternative method.
Content Type Journal Article
Category STRUCTURE OF CHEMICAL COMPOUNDS, METHODS OF ANALYSIS AND PROCESS CONTROL
Pages 1-4
DOI 10.1007/s11094-011-0609-8
Authors
A. M. Aliev, Azerbaidzhan Medical University, Baku, Azerbaidzhan
G. M. Babazade, Azerbaidzhan Medical University, Baku, Azerbaidzhan
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NO2 group at 5th position of benzothiazole ring (12a–f) increased the antitubercular activity whereas introduction of 
