To identify the most active antiepileptic compound, we undertook a structure-based design approach that used three-dimensional structural model of the ?-aminobutyrate aminotransferase and GABA-AT protein, and molecular docking simulations of newer agents, 4-bromophenyl-substituted aryl semicarbazones, sulphonamide derivative-hydrophobic domain, 1,2,4-thiadiazoles, p-nitrophenyl semicarbazones and aryl semicarbazones groups. Autodock 4.0 and visual molecular dynamics VMD were used for docking and ligand–protein interactions, respectively. Based on these in silico methods, a new lead compound has been identified on the basis of strong interactions and MES value, which leads to the formation of structural analogues from the active lead compound. These new structural analogues can be useful for the design of future targets and development of new drugs.

A new series of pyrano[4,3-b]chromene and benzopyrano[3,2-c]chromene derivatives have been synthesized via microwave-assisted one-pot, three-component reaction of N-allyl quinolones, cyclic ?-diketones, and 4-hydroxy-6-methyl-2H-pyran-2-one/4-hydroxy coumarin in the presence of catalytic amount of ceric ammonium nitrate under solvent-free condition. The protocol offers expeditious and solvent-free synthesis with excellent yield to furnish fused chromenes for their antimicrobial activity. The chemical structures of the synthesized compounds were elucidated by ¹H NMR, ¹³C NMR, FT-IR, elemental analysis, and mass spectral data. All the compounds were screened against a representative panel of pathogenic strains by broth micro dilution minimum inhibitory concentration method. Among these derivatives, compounds 6i, 6k, 6l, and 6m were found to have admirable activity when compared to the standard drugs.

The mTOR-mediated PI3K/AKT/mTOR signal transduction pathway plays a key role in a broad spectrum of cancers. In the present article, QSAR and pharmacophore studies were carried out using a series of 61 benzothiazole class of PI3K? inhibitors to characterize molecular features and structural requirements crucial for biological interaction. QSAR study performed using TSAR 3.3 by multiple regression analysis and partial least square methods identified inertia moment-1-size, kier chiv5 (path) index, and number of H-bond donors as important descriptors responsible for PI3K? inhibitory activity. Further analysis of pharmacophore model by means of Phase module of Schrodinger revealed that two hydrogen-bond acceptors, one hydrogen-bond donors, and two hydrophobic aromatic rings as crucial molecular features that predict binding affinity for high-affinity ligands to the PI3K? enzyme. These observations provide important insights to the key structural requirements of these molecules for potent PI3K? inhibition. Excellent statistical results of developed models strongly suggest that these models are reasonable for the prediction of the activity of new inhibitors and in future drug design.

A new series of phenoxyacetic acid bearing pyrazoline derivatives 7a–k were synthesized and characterized by IR, ¹H-NMR, and mass spectral data. The investigated compounds were screened for their diuretic activity by standard Lipschitz method. Furthermore, the series under investigation were assessed for their drug-likeness by suitable software programs. These compounds were found to have promising results against a given set of diuretic parameters, i.e., cumulative urine output, diuretic activity, diuretic action, and Lipchitz values. Nevertheless, compounds 7d, 7h, 7i, and 7k bearing electron withdrawing group (Cl^?) showed pronounced diuretic propensity than the standard furosemide.

1-(1-Alkyl-6-substituted-1H-benzimidazol-2-yl)-naphthalen-2-ols have been synthesized using o-phenylinediamine and naphthaldehyde in the presence of sodium hydride and THF. 1-(1-Alkyl-6-substituted-1H-benzimidazol-2-yl)-naphthalen-2-ols were evaluated for the analgesic activity by tail flick method in rats. Synthesized1-(1-alkyl-6-substituted-1H-benzimidazol-2-yl)-naphthalen-2-ols in doses of 50 mg/kg increased the pain threshold significantly after 0, 30, 60, 90, and 120 min of administration in the tail flick model. Compounds B₃a, B₂b, and B₁b showed time-dependent action in all the experimental models. The present study indicates that Compounds B₃a, B₂b, and B₁b show analgesic properties.

Mn(II)-, Fe(II)-, Co(II)-, Ni(II)-, and Zn(II)-Schiff base complexes containing anthranilic acid and aldoses as part of the base were prepared and characterized by microanalytical, thermogravimetric, and spectroscopic data. The complexes were found to be four-coordinate, anhydrous, and ML₂ type. The spectral and magnetic data indicate a tetrahedral geometry for Mn(II) and Fe(II) complexes, and a planar geometry for Co(II), Ni(II), and Zn(II) complexes. Mn(II) and Zn(II) complexes showed a significant anti-inflammatory activity against kaolin-paw-edema. All the complexes exhibited selective inhibition of COX-2 in two different cell models.

N-Furfurylideneanilines and N-arylamino(2-furyl)methylphosphonates with tolyl and anisyl moieties were synthesized by the addition of phosphites to azomethine bond of corresponding Schiff bases and their NMR spectroscopic properties were investigated. Then, they were analyzed in the point of view of their influence on KYSE 30, KYSE 150, and KYSE 270 esophageal cancer cell lines and on immortalized esophageal cell line HET 1 A as a control group. Toxicity was evaluated by MTT assay. Among 11 compounds, a few of them demonstrated influence on cancer cells being neutral toward the control, but only one aminophosphonate had IC₅₀ lower than 100 ?M and acted as a potential anticancer drug. Some approaches to structure–activity relation were performed.

Natural (?)-(aS, 7S)-colchicine, an alkaloid and toxic natural product is a secondary plant metabolite, obtained from Colchicum autumnale also known as ‘meadow saffron’. Colchicine, among the Indian medicinal plants, is contained in the corms of Colchicum luteum and the seeds of Iphigenia, to the extent of about 0.25 and 0.9 % respectively. These plants are not available in sufficient quantities to warrant any commercial utilization. Natural (?)-colchicine has only one stereogenic centre: carbon-7. The biosynthesis of colchicine involves amino acid precursors, phenylalanine and tyrosine. It is used to treat rheumatic complaints, especially gout, also prescribed for its cathartic and antiemetic effects and also in initial treatment for pericarditis. It is also being investigated for its use as an anti-cancer drug. Colchicine itself is too toxic for human use as an anti-tumour drug and hence its derivatives have been used. Colchicine poisoning has been reported in patients with kidney or liver failure. In neurons, axoplasmic transport is disrupted by colchicine. It is used widely off-label by naturopaths for a number of treatments, including the treatment of back pain and also used as an anti-inflammatory agent for long-term treatment of Behcet’s disease.

New series of 2,5-dihydroxyphenyl-1,3-thiazoles 4a–l was synthesized by reacting 2,5-dihydroxyphenacyl bromide with various 4-aryl thiosemicarbazones 3a–l that on oxidation with ferric chloride yielded the corresponding N ¹-substituted benzylidene-N ²-[3-aryl-4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-ylidene]hydrazines 5a–l. They were evaluated for antibacterial activity against Staphylococcus aureus and Bacillus subtilis as Gram-positive bacteria, Escherichia coli and Pseudomonas aeruginosa as Gram-negative bacteria. They were also evaluated for their in vitro antifungal potential against Candida albicans. Almost all tested compounds were found to possess variable degrees of antimicrobial activity. The obtained data revealed that compounds 4b–h and 5e, 5f and 5l exhibited promising antimicrobial activity against the tested organisms of which compound 4b proved to be the most active.

The effectiveness of the essential oil of Salvia tomentosa Miller was assessed on two important pest insects and seven pathogenic bacteria. The essential oil of aerial parts of this plant was hydro-distillated using a clevenger-type apparatus (yield 0.31 % v/w) and constituents were determined using GC–MS analysis. ?-pinene (37.28 %) and ?-pinene (5.73 %) were the predominant chemical constituents, followed by trans-pinocarveol (3.05 %), myrtenol (2.81 %), caryphyllene oxide (2.68 %), d-camphor (2.08 %). The complete mortality was determined at above doses of 50 ?l L^?1 air on Acanthoscelides obtectus (Say) adults. However, the essential oil in concern caused 83.34 and 100 % mortality at higher doses (150 and 200 ?l L^?1 air) against Tribolium castaneum (Herbst) adults. The essential oil also revealed significant bacteriostatic and bactericidal activities against Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Micrococcus luteus, Escherichia coli, Enterobacter aerogenes and Yersinia enterocolitica. The essential oil of S. tomentosa in concern can be used as a potential insecticide and bactericidal agents in food applications and agricultural commodities and/or other fields.

New indole analogues containing pyrido[2,3-d]pyrimidin-4-(3H)-ones (3a–i), pyrazolo[3,4-b]pyridin-3-amines (4a–i) and pyrido[2,3-d]pyrimidin-4-amines (5a–i) were synthesized using appropriate synthetic routes. These newly synthesized compounds were screened for their antimicrobial and antioxidant activities. Compounds 3a, 3g, 4c, 4h, 4i, 5a, 5c and 5f exhibited good antibacterial and antifungal activities. The compounds 3b, 3c, 3g, 4a, 4h, 4i and 5a exhibited good radical scavenging activity. Compounds 3a and 4d exhibited good metal chelating activity compare with standards.

Pyrazolo[3,4-d]pyrimidine analogues were synthesized by treating 3-phenyl-1H-pyrazolo[3,4-d]pyrimidine-4-amine with different sulfonyl chlorides and triethylamine in dry dichloromethane. The structure of all the compounds was elucidated by spectral data and their purity was confirmed by elemental analysis. In vitro antiamoebic activity was performed against HM1:IMSS strain of Entamoeba histolytica and two compounds, 4 (IC₅₀ = 0.57) and 6 (IC₅₀ = 0.68), were found better inhibitors than the reference drug metronidazole (IC₅₀ = 1.80). Further, both the compounds (4 and 6) were low cytotoxic against the human breast cancer MCF-7 cell line in the concentration range of 2.5–250 ?M. These preliminary results reveal that pyrazolo[3,4-d]pyrimidine analogues could help in designing better molecules with enhanced antiamoebic activity.

In this article, we synthesized a series of novel 1-benzyl-5(3)-p-tolyl-1H-pyrazole-3(5)-carboxylic acid derivatives and characterized by IR, ¹H NMR, and mass spectroscopy. Compounds were evaluated for their in vivo analgesic and anti-inflammatory activity using the p-benzoquinone-induced writhing test and the carrageenan-induced paw edema model, respectively. Out of 14 compounds tested, 7a, 7c, 7e, 7f, 7i, 8a–b, and 8f–g exhibited potent analgesic and/or anti-inflammatory activity as compared to reference drugs aspirin and indomethacin. Anticancer activity of these compounds was assessed against five cancer cell lines with the MTT assay (HL-60, human promyelocytic leukemia cells; HeLa, human cervical cancer cells; Raji, human B lymphocyte cell line; MCF7, human breast adenocarcinoma cell line; MDA-MB-231, estrogen-independent human breast cancer cell line). Compounds 7a, 8a, and 8b with high anti-inflammatory activity, and also 7d and 7j with mild anti-inflammatory activity exhibited promising anticancer activity against some selected cell lines.

A series of 5-((3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (4a–f) and dihydro-5-((3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxopyrimidine-4,6(1H,5H)-dione (5a–f) derivatives were synthesized by the condensation of 3-(2-oxo2H-chromen-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (3a–f) with barbituric acid and thiobarbituric acid in acetic acid under microwave irradiation method. The newly synthesized compounds were evaluated for their antibacterial activity against Bcillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeoginosa, and Klebsiella pneumoniae. All the compounds were found to be moderately active against used microorganisms, whereas compounds (4d) and (4e) exhibited good antifungal activity against Aspergillus niger.

4-(4-Oxo-4H-3,1-benzoxazin-2-yl)phenyl-4-methylbenzenesulfonate (2) was prepared and reacted with some primary aromatic amines, e.g., aniline, p-chloro aniline, p-methoxy aniline, p-amino benzoic acid and p-amino acetophenone. It reacted also with some heterocyclic amines, e.g., 2-aminothiazole, 2-aminobenzothiazole, 5-amino-4-phenylazo-2,4-dihydropyrazol-3-one and 3-amino-2-methylquinazolinone and with diamines; e.g., o-phenylenediamine, p-phenylenediamine, ethylenediamine, semicarbazide hydrochloride and thiosemicarbazide under different conditions. On the other hand, compound (2) reacted with both sodium azide and active methylene compounds, e.g., ethylcyanoacetate and ethylacetoacetate to give (19) and (20), respectively. All new prepared compounds were subjected to antimicrobial activity evaluation.

There are limited studies centring on the potential of thiazolidin-4-ones as anticancer agents. In this study, a new series of 2-(3-substituted-1H-pyrazol-4-yl)-3-(3-substituted-5-sulfanyl-1,2,4-triazol-4-yl)-1,3-thiazolidin-4-one (4a–o) have been synthesized by cyclo-condensation reaction of 5-substituted-4-[(3-substituted-1H-pyrazol-4-ylmethylidene)amino]-2H-1,2,4-triazole-3-thione (3a–o) and thioglycolic acid. The structures of all the synthesized compounds were confirmed by elemental analysis, spectral techniques like IR, ¹H NMR, and mass spectroscopy. Few compounds exhibited dose-dependent cytotoxic effect in MTT assay in human breast cancer (MCF-7) cells. Apoptotic degradation of DNA due to action of potent thiazolidin-4-ones was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). A concentration-dependent increase in tail length and olive tail moment was observed when treated with thiazolidin-4-ones. In vitro antioxidant studies like DPPH and ABTS-free radical scavenging assays-indicated moderate activity of thiazolidin-4-ones.

Antioxidants are emerging as potential prophylactic and therapeutic agents which scavenge free radicals otherwise reactive oxygen species and prevent the damage caused by them. Free radicals have been associated with pathogenesis of various disorders like cancer, diabetes, cardiovascular diseases, autoimmune diseases, neurodegenerative disorders and are implicated in aging. Chromones and their derivatives display important biological activities such as anti-tumor, anti-hepatotoxic, anti-inflammatory, anti-spasmolytic, oestrogenic and antibacterial activities, in particular the antioxidant behavior of these compounds continue to draw attention of researchers. In the present communication a series of halo substituted 2-styrylchromones 4a–4k were prepared and tested for the antioxidant activity by using DPPH (1, 1 diphenyl 2, picryl hydrazyl) method, and among the synthesized compounds 4e and 4h shows strong antioxidant activity while remaining compounds show antioxidant activity in the normal range.

Linum album is a herbaceous medicinal plant that contains some lignans with antiviral and anticancer properties such as podophyllotoxin (PTOX) and 6-methoxy podophyllotoxin (MPTOX). In this research, hairy root cultures of L. album were established by transformation with Agrobacterium rhizogenes strains LBA9402, A4, AR15834 and Agrobacterium tumefaciens strain C58C1 (pRiA4). The presence of PTOX and MPTOX in the hairy roots was verified by ESI/MS in positive ion mode. MPTOX was confirmed and its enantiomer determined by nuclear magnetic resonance spectroscopy and circular dichroism spectroscopy, respectively. PTOX and MPTOX production was determined by HPLC, in different lines of hairy roots. The results showed that all obtained hairy root lines produced higher yield of lignans than mother plant roots. In addition, the lignan content in the roots derived from A. rhizogenes strain LBA9402 was higher than in those obtained from A. tumefaciens strain C58C1.

In search of novel antiviral and anticancer agents with promising pharmacotoxicological profile, a study was initiated to synthesize new 2-thioxo-4-thiazolidinones as well as 2-phenylimino-4-thiazolidinones substituted with benzimidazole ring system. The compounds were screened primarily for their antiviral as well as anticancer activities. The synthesis of some novel 5-substituted thiazolidinones was also described. None of the tested compounds showed inhibitory activity against Hepatitis C virus replication. Two 2-phenylimino-4-thiazolidinone derivatives (9a and 10) exhibited significant antiproliferative activity against human colon carcinoma cell line HCT 116 and human hepatocellular carcinoma HEPG2 cell line, respectively. Results also indicated that six thiazolidinone derivatives (5a, 5d, 5e, 5f, 5h, and 9d) showed moderate antiproliferative activity against human breast adenocarcinoma cell line MCF7 in comparison to the standard drug Doxorubicin. Moreover, a docked pose of the most potent three cytotoxic compounds 5a, 5h, and 9d against MCF7 was obtained bound to Human N-acetyl transferase1 NAT1 binding pocket by molecular operating environment module.

In this study, novel series of chalcone derivatives, namely, 4-[4-(3-phenyl-acryloyl)-phenylamino]-chromen-2-one (5a–k) have been synthesized from the intermediate 4-(4-acetyl-phenylamino)-chromen-2-one (4). Cyclization reaction of chalcone (5a–k) with hydrazine hydrate, guanidine nitrate, and malononitrile gives the corresponding 4-[4-(1-acetyl-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-phenylamino]-chromen-2-one (6a–k), 4-[4-(2-amino-6-phenyl-pyrimidin-4-yl)-phenylamino]-chromen-2-one (7a–k), and 2-amino-6-[4-(2-oxo-2H-chromen-4-ylamino)-phenyl]-4-phenyl-nicotinonitrile (8a–k) derivatives were synthesized. The newly synthesized compounds were evaluated for their antimycobacterial activity and antimicrobial activity against eight bacteria (S. aureus, B. cereus, E. coli, P. aeruginosa, K. pneumoniae, S. typhi, P. vulgaris, and S. flexneri) and four fungi (A. niger, C. albicans, A. fumigatus, and A. clavatus).

The Schiff’s bases 3a–3h were synthesized by reacting substituted/unsubstituted aromatic aldehydes 2a–2h with 1-(2-aminoethyl)-piperazine 1. A series of novel aryl-3-(2-piperazin-1-ylethyl)-1,3-thiazolidin-4-one 4a–4h and 3-chloro-1-{2-[4-(chloroacetyl)piperazin-1-yl]ethyl}-4-arylazetidin-2-one 5a–5h were synthesized from the Schiff’s bases of 1-(2-aminoethyl)-piperazine 3a–3h. The structures of synthesized compounds were confirmed by analytical (C, H, and N) and spectral (FT-IR, ¹H NMR, ¹³C NMR, and Mass) data. The compounds 4a–4h and 5a–5h were screened for antimicrobial activity. The compounds 4a, 4d, 4f, 4g, 5a, 5d, 5f, and 5g exhibited substantially significant antibacterial as well as antifungal activity.

Molecules with potent estrogenic activity are ~270 Å³ hydrophobic structures that encompass two hydroxyls among which is at least one phenol. However, compounds with only one phenol or devoid of such a ring have been shown to enhance ER?-mediated transcription at concentrations much larger than those measured with E₂. In this context, we show here that benzopyrans sharing one hydroxyl/methoxyl and containing an additional benzylidenyl or a spirocyclohexyl motif are able to induce ERE-dependent transcription in breast carcinoma cells.

A novel series of pyrimidine-benzenesulfonamide derivatives as potential cyclin-dependent kinase 2 inhibitors were designed depending upon the molecular docking simulation study. This study was preceded by modification and optimization of the lead compound 4-(2-amino-4-methylthiazol-5-yl)-N-(3-nitrophenyl) pyrimidin-2-amine. The target proposed compounds were synthesized using the derivative 6-(3,4-dimethoxyphenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (1) as a key starting compound. Some of the synthesized derivatives were selected as representative examples to evaluate their anti-proliferative activity against cultured human Hela cell line using doxorubicin as a reference drug and the results obtained were correlated with the data of molecular modeling simulation study. The structures of the novel derivatives were confirmed on the bases of micro-analytical and spectral data.

Benzimidazole is an interesting heterocyclic compound because it is found in various drugs such as bifeprunox, pimozide, droperidol, etc. The efficacy of substituted benzimidazoles in the treatment of psychoses is well known. Substituted benzimidazole moieties are established pharmacophores in schizophrenia chemotherapy. Benzimidazole derivatives have proven to be of great potential in determining a wide range of activity by binding to various receptors. In addition, piperazinyl moieties linked to benzimidazole enhances the activity at the DA receptors to a greater extent. Various routes have been adopted for the synthesis of derivatives having comparable anti-psychotic activity at various receptors. Dopamine receptors have the potential to mediate activity to varying extent through the binding of ligands, upon it. In this review, binding affinity values of various substituted parent compounds to various dopamine receptors as well as few 5-HT receptors with antipsychotic activity have been tabulated and the synthetic scheme of the same has been shown. This review is summarized to know about various benzimidazolo-piperazinyl ligands that have potential to bind at the dopamine receptors.

A novel and efficient synthesis of pyrogallol moiety through a copper(I)-mediated C–O bond forming reaction is described. In particular, syntheses of 3,4,5-trihydroxyphenethyl alcohol and its methyl derivative are reported. Particular attention to dimethyl carbonate as an eco-friendly solvent/reactant has been paid, in order to improve the eco-compatibility of the whole synthetic pathway. Furthermore, the genotoxicity, cytotoxicity and the antioxidant activity of 3,4,5-trihydroxyphenethyl alcohol and its methyl derivative have been investigated.

Keeping the objective to build up a new structural class of potent antimicrobials and antituberculosis agents, a series of potentially active quinoline-based azetidinone and thiazolidinone analogues has been synthesized by a simple and efficient synthetic protocol. The thione nucleus formed from 2-chloroquinoline-3-carbaldehyde using sodium sulphide in DMF followed by reaction with various substituted amine to form the corresponding Schiff base intermediates. Attempt has been made to derive final azetidinone and thiazolidinone analogues from Schiff bases by using chloroacetyl chloride and 2-mercapto acetic acid, respectively. Newer analogues were characterized by IR, ¹H NMR, ¹³C NMR spectroscopy and elemental analyses. The newly synthesized analogues were then examined for their antimicrobial activity against some bacterial and fungal strains as two Gram ?ve bacteria (Escherichia coli MTCC 739, Pseudomonas aeruginosa MTCC 741), two Gram +ve bacteria (Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 430) and two fungal species (Aspergillus niger MTCC 282, Candida albicans MTCC 183) to develop a novel class of antimicrobial agents and The final compounds were tested for in vitro antituberculosis activity against Mycobacterium tuberculosis. Streptomycin, Isoniazid, Rifampicin and Ethambutol were used as standards in this test. These observations provide some predictions to design further antibacterial and antituberculosis active compounds prior to their synthesis according to molecular modeling studies.

Sodium-dependent glucose cotransporter 2 (SGLT2) have emerged as a novel drug target for hyperglycemia, a major complication of type 2 diabetes, with a multitude of therapeutic potential for their inhibitors. A series of N-?-d-xylosylindole derivatives has been reported as SGLT2 inhibitors. Therefore, to determine the structural requisite of these SGLT2 inhibitors, 3D pharmacophore models and atom-based 3D QSAR models have been developed using the PHASE module of Schrödinger. The best six-featured pharmacophore hypothesis with two hydrogen bond acceptors, two hydrogen bond donors, one hydrophobic features, and one aromatic ring yielded a 3D QSAR model. The derived model have significant PLS values as R ² = 0.9527, correlation coefficient of training set, and Q ² = 0.9045, correlation coefficient of test set, indicating the model have good predictive power. The results provide detailed insights of N-?-d-xylosylindole derivatives which can afford guidance for rational drug design of novel potent SGLT2 inhibitors.

Chronic hyperglycaemia is a major initiator of diabetic cardiovascular complications and microvascular complications such as retinopathy, neuropathy and nephropathy. Experimental results reveal liaison between cardiovascular disease and diabetic complications. Of the various targets, PKCs were identified to be specifically involved in diabetic complications, of which PKC?II isoform was found to play a significant role. Although the benefit of PKC?II is immense, not a single molecule has been approved yet for diabetic treatment. Because protein kinases share a high degree of similarity in both structure and functions, developing a highly specific inhibitor has been a challenging task. In this study, we have designed peptidomimetics based on autoinhibitory domain as this domain has a recognition motif specific for each isoform to resolve the specificity issue and validated the designed peptidomimetics by molecular docking. This study has provided useful insights into molecules that may be useful for diabetic complications.

The QSAR studies were performed on a series of 2,3,5-trisubstituted 4,5-dihydro-4-oxo-3H-imidazo [4,5-c] pyridine derivatives as angiotensin II AT₁ receptor antagonists activity to find out the structural features requirements for the antihypertensive activity. The QSAR study was carried out on V-life Molecular Design Suite software and the derived best QSAR model by partial least square principal component regression and multiple linear regression method showed variation in biological activity. The statistically best significant model with high-correlation coefficient (r ² = 0.9425) was selected for further study and the resulted validation parameters of the model, cross-validated correlation coefficient (q ² = 0.7786 and pred_r ² = 0.8562) show the model has good predictive activities. The model showed that the parameters SdssCcount, SssNHcount, and SaaaCcount and H_Donor count are highly correlated with angiotensin II AT₁ receptor antagonists activity of 2,3,5-trisubstituted 4,5-dihydro-4-oxo-3H-imidazo [4,5-c] pyridine derivatives. Partial least square (PLS) methodology coupled with various feature selection methods viz. stepwise, simulated annealing and genetic algorithm were applied to derive 3D-QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. Molecular field analysis was used to construct the best 3D-QSAR model-7 using k-nearest neighbor (kNN) method, showing good correlative and predictive capabilities in terms of q ² = 0.8316 and pred_r ² = 0.8152. Both 2D-and 3D-QSAR study of such derivatives provide guidance for further lead optimization and designing of potent anti-hypertensive agents.

Binding site analysis of flavonoids derivatives indicated that Arg152, Trp178, Ile222, Glu227, and Ala246 were the key residues in the active pocket of 1nnc. Main influencing factors of interactions between flavonoids derivatives and neuraminidase (NA) were hydrogen bond and electrostatic. Meanwhile, 3D-QSAR models of flavonoids derivatives were constructed to understand chemical–biological interactions governing their activities toward NA. The developed 3D-QSAR models were robust and had good predictive capabilities. R ², Q ², R _test², and Q _ext² of the CoMFA and CoMSIA models were 0.816 and 0.929, 0.607 and 0.750, 0.507 and 0.642, and 0.478 and 0.568, respectively. Moreover, hydrogen bonds and electrostatic factors highly contributed to inhibitory activity, which were unanimous in the docking results. In addition, based on the most active sample ID33, seven new compounds with high inhibitory activity and docking score were obtained.

As a basis for predicting structural features that may lead to the design of more potent and selective inhibitors of urease, the three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were carried out on a series of 30 bis-coumerine analogs, which are known urease inhibitors. Five different properties: steric, electrostatic, hydrophobic, H-bond donor, and H-bond acceptor, assumed to cover the major contributions to ligand binding, were used to generate the 3D-QSAR model. A significant cross-validated correlation coefficient q2 (0.51), r ² (0.962) for CoMSIA were obtained, indicating the statistical significance of this class of compounds. Actual urease inhibitory activities of this class, and the predicted values were in good agreement with the experimental results. This model offer insight into the structural requirements for activity of bis-coumerine analogues as urease inhibitors, since there is only speculative knowledge of their target in protein.

New azetidinone and thiazolidinone class of bioactive agents based on quinoline nucleus have been synthesized. 2-Chloroquinoline-3-carbaldehyde reacted with various substituted amine to form the corresponding Schiff base intermediates. We have derived final azetidinone and thiazolidinone analogues from Schiff bases using chloroacetyl chloride and 2-mercaptoacetic acid, respectively. The newly synthesized analogues were then examined for their antimicrobial activity against some bacterial and fungal strains as two gram ?ve bacteria (Escherichia coli MTCC 739 and Pseudomonas aeruginosa MTCC 741), two gram +ve bacteria (Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 430), two fungal species (Aspergillus niger MTCC 282 and Candida albicans MTCC 183) as well as against Mycobacterium tuberculosis strain H37Rv to develop a novel class of bioactive agents. The results of bioassay showed that some of the newly synthesized azetidinones and thiazolidinones emerged as lead molecules with excellent MIC (mg/mL) values against mentioned microorganisms compared to standard drugs. The structure of the final analogues has been confirmed on the basis of IR, ¹H NMR, ¹³C NMR, and elemental analysis.

The aim of this work was to investigate the antibacterial and antifungal activities of novel d-amino acid-Schiff bases including fluorine atom and their Cr(III) and Ni(II) complexes. All these substances have been examined for antibacterial activity against pathogenic strains Listeria monocytogenes 4b ATCC19115, Staphylococcus aureus ATCC25923, Escherichia coli ATCC1280, Salmonella typhi H NCTC 901.8394, Brucella abortus (A.99, UK-1995) RSKK03026, Staphylococcus epidermis sp., Micrococus luteus ATCC9341, and Shigella dysenteria typ 10 NCTC 9351, and antifungal activity against Candida albicans Y-1200-NIH, Tokyo. The antimicrobial test results of these amino acid-Schiff base complexes exhibited better activity than some known antibiotics. In particular, diamagnetic Ni(II) complexes were more potent bactericides than all of the substances synthesized.

Leishmaniasis is a detrimental disease caused by the parasite Leishmania which has a unique redox metabolism involving trypanothione. Trypanothione delivers reducing equivalents which in turn saves the parasite from oxidative damage and is also utilized in the formation of deoxyribonucleotides. The polyamine biosynthesis pathway starts with the conversion of ornithine to spermidine, precursor of trypanothione, by ornithine decarboxylase. Thus, targeting ornithine decarboxylase would inhibit formation of spermidine and subsequently trypanothione, affecting the growth and survival of Leishmania. This enzyme could be a good drug target to combat leishmaniasis. In the current study, we have predicted the 3D structure of Leishmania donovani ornithine decarboxylase. Moreover, we have conducted structure-based virtual screening against the enzyme in an attempt to find potential leishmania-specific inhibitors. Interactions of the leishmanial enzyme with the inhibitors have also been investigated to identify functionally important residues.

Asparagus racemosus is used in the Indian traditional system of medicine for improving the general state of health and stress-related immune disorders. Most of the synthetic chemotherapeutic agents available today are immunosuppressants and exert variety of side effects. To overcome these undesired effects of chemotherapeutic agents, botanical-based immunomodulators are often employed as adjuvant therapy. In the present study, immunomodulatory activity of two steroidal saponins shatavaroside A (1) and shatavaroside B (2), isolated from Asparagus racemosus, have been evaluated using polymorphonuclear leucocyte function test. The activity was further confirmed using more sensitive assays such as nitroblue tetrazolium, nitrous oxide, and chemiluminescence assays. Both steroidal saponins were found active at nano concentration (5 ng/ml) and can act as potent immunostimulants.

A new monomer, m-keto acetyl naphthalene acrylic acid (KANAc) was synthesized from reactants of maleic anhydride and 1-acetyl naphthalene. This monomer was polymerized by exposure to ?-rays ⁶⁰Co. The effects of dose, dose rate, monomer concentration, and temperature on polymerization yield have been investigated. KANAc and its poly(KANAc) were characterized by different techniques. The results indicated that the average molecular weights ranged from 1.1 to 7 × 10⁵ g/mol and having a good stability. The poly(KANAc) has showed broad spectrum antimicrobial activity. Minimal inhibitory concentration (MIC) values ranged from 96 to 186 ?g/ml. At MIC and 0.5× MIC concentrations, poly(KANAc) exerted variable effects on 24.4 Gy in vitro ?-irradiated and non-irradiated tested strains. Poly(KANAc) altered cell membrane permeability, induced genomic DNA damage and adverse effects on total protein. Furthermore, it proved to induce in vitro cytotoxicity against different human carcinoma cell lines with 50% inhibitory concentrations (IC₅₀) values in the range of 9.9–32.2 ?g/ml. The outcome results have been good and promising in both antimicrobial and antitumoral fields.

Dipeptidyl peptidase IV (DPP-IV) is a potential drug target for type-2 diabetes and DPP-IV inhibitors are known to efficiently improve glucose tolerance. In the present study, pharmacophore model for a set of 29 DPP-IV inhibitors was generated by ligand-based pharmacophore generation process. The best hypothesis, hypo 1, consisting of four chemical features, namely, one hydrogen bond donor, one hydrogen bond acceptor, one hydrophobe and one ring aromatic was validated by cost function analysis, test set prediction and Fischer test. The validated pharmacophore model was then used for searching new lead compounds from Maybridge and NCI database. Four compounds (CD01797, CD06202, CD02493, and AW01077) from Maybridge database and three compounds (NSC997, NSC2450, and NSC5815) from NCI database were identified as structurally diverse druggable novel leads with nM activity against DPP-IV.

Some of new 3-(4-chlorophenyl or 4-fluorophenyl)-6-iodo-4-oxo-3,4-dihydroquinazoline derivatives having a Schiff bases, oxazolone, imidazolidine, pyrazolidine, pyridine, pyrimidine, and various substituted C-2 have been synthesized. Screening for some selected compounds was carried out for their potential anti-inflammatory and analgesic activity.

A series of (3-phenyl-5-(1-phenyl-3-aryl-1H-pyrazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanones was synthesized by condensing suitably substituted chalcones, i.e., 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-ones, and isoniazid in acetic acid. The structure of newly synthesized compounds has been established on the basis of analytical and spectral data. The new compounds were screened for antimicrobial activity and most of them showed good activity comparable with that of standard drugs ciprofloxacin and fluconazole. Compounds containing methoxy group showed high antimicrobial activity.

A series of new phthalides of pharmacological interest were synthesized by a protocol involving condensation of two ?-keto acids, 2-(4-isopropylbenzoyl)benzoic acid (1a) and 2-(4-isopropyl-3-nitrobenzoyl)benzoic acid (1b) with phenolic compounds in the presence of catalytic quantity of concentrated sulphuric acid. The method is simple, efficient, economical and environmentally benign as the reaction is carried out under solvent free condition attempting a green approach. Structural characterization of these newly synthesized compounds was accomplished by IR, UV, ¹H NMR, ¹³C NMR, Mass spectral data, elemental analysis and chemical reactions. Some of the synthesized phthalides were found to exhibit antifungal and antibacterial activity against various human pathogenic bacterial and fungal strains.

Amebiasis is a major threat to the public health that causes tens of thousands of deaths per year. In order to better rationalize the discovery of more potent anti-amebic agents, three-dimensional quantitative structure–activity relationship studies were conducted on a large number (six sets) of anti-amebic thiosemicarbazones and thiocarbamoylpyrazolines using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis and the topomer CoMFA methods, in addition to the 3D-dependent Eigen value analysis method. The generated models were subject to internal, external, and cross validation statistical tests to judge their respective qualities. Herein, the best alignment approach was described and the models’ profiles were analyzed to give a structural insight of more potent antiamebics.

A series of 3,4-dimethoxyphenylethylamine derivatives was prepared from Baylis–Hillman (BH) adducts. The effect of these compounds on the proliferation of breast cancer cell lines (MCF-7) and the corresponding Doxorubicin (Dox) resistant cell lines (MCF-7/ADR) was studied. Aminoalcohols 1a–d were obtained from the Michael addition reaction of 3,4-dimethoxyphenylethylamine and BH adducts. For the preparation of unsaturated amines 2a–d, BH adducts were converted into allylic bromides by treatment with HBr in acidic solution. N-nucleophile introduction could be controlled by the choice of solvent furnishing the corresponding amines 2a–d. A third class of amines (3a–c) was prepared by hydrogenation reaction of amines 2a–d. In respect of the biological evaluation, some of the synthesized compounds exhibited moderate inhibitory effect on the cell growth. In addition, in MCF-7/ADR cell lines, the antiproliferative effect of Dox shifted from 5 to 88 % when co-administrated with compound 2b.

A Bayesian regularized artificial neural network (BR-ANN) model was developed for modeling and accurate prediction of necroptosis inhibitory activities of [1,2,3] thiadiazole and thiophene derivatives as potent tumor necrosis factor-?-induced necroptosis inhibitors. The chemical structure of each compound was converted to 1,481 molecular descriptors by Dragon software. Among these, only seven descriptors relating the activity data to the molecular structures were selected as the significant ones. The best BR-ANN model was a three layer feed forward network with the 7-4-1 architecture. Prediction ability of the proposed model was evaluated by prediction of pEC₅₀ of some compounds in the external (test) data set. The mean square error, mean absolute error, correlation coefficient (R), and mean relative error for the test set were 0.0214, 0.126, 0.978, and 2.475, respectively. The results obtained show the superior prediction ability of the proposed model in the prediction of necroptosis inhibitory activities.

Four new sulfated steroidal compounds, sodium 3-hydroxy-6-hydroximinocholestane 3-sulfate (7a), sodium 3-hydroxy-6-hydroximinostigmastane 6-sulfate (7b), sodium 3-hydroxy-6-hydroximinocholest-4-ene 3-sulfate (10a), and sodium 6-hydroxy-3-hydroximinocholestane 6-sulfate (16) had been synthesized using cholesterol or stigmasterol as starting materials by different synthetic methods. The synthetic compounds were characterized by their analytical and spectral data, and their antiproliferative activity against MGC 7901 (human gastric carcinoma cell line), HeLa (human cervical carcinoma cell line), and SMMC 7404 (human liver carcinoma cell line) were investigated. The results showed that the compounds exhibited a remarkable cytotoxicity against HeLa tumor cells in vitro and 7a displayed a better cytotoxicity than cisplatin (a positive contrast).

Enzymes of shikimate pathway, dehydroquinase and shikimate kinase represent comparatively newer targets for antitubercular research. Molecular hybridization approach was implemented by integrating the essential features of inhibitors acting on these enzymes of shikimate pathway. Considering the flexibility of alicyclic ring of reported dehydroquinase (DHQ) inhibitors and triazole ring, key feature of the virtual hits of Mtb shikimate kinase, a series of structurally novel, substituted 4H-1,2,4-triazol-3-yl cycloalkanols were designed as antimycobacterial agents. Docking studies of the molecules was carried out on the enzyme DHQ. All the synthesized compounds exhibited promising activity (MIC 0.59–15.5 ?g/ml) against H₃₇Rv strains of Mycobacterium tuberculosis using resazurin microtiter assay. Five of the evaluated compounds exhibit MIC < 1 ?g/ml. CC₅₀ values indicate compounds are non-toxic, with selectivity indices >28. These compounds could serve as leads for further optimization to obtain novel antimycobacterial agents.

A series of 1-(aryloxypropyl)-4-(chloroaryl) piperazines have been synthesized based upon their physicochemical similarity with respect to standard atypical antipsychotic drugs and their potential to cross the blood–brain barrier (log BB) as calculated by appropriate software programmes. The target compounds were evaluated for atypical antipsychotic activity in apomorphine-induced mesh climbing and stereotypy assays in mice. The compounds 8, 9 and 10 bearing hydrogen bond acceptor substituents have emerged as important lead compounds showing higher efficacy along with potential atypical antipsychotic profile.