Javed Sheikh

QSAR and CoMFA studies of biphenyl analogs of the anti-tuberculosis drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo [2,1-b][1,3]oxazine (PA-824)

With the purpose of designing new chemical entities with enhanced inhibitory potencies against Mycobacterium tuberculosis, the 3D-QSAR CoMFA study carried out on biphenyl analogs of the tuberculosis drug, (6S)-2-nitro-6-{[4-trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824), is presented here. The developed model showed a good correlative and predictive ability. The final QSAR models as well as the information gathered from 3D contour maps should be useful for the design of novel PA-824 analogs having improved anti-TB activity.

Computational evaluation and experimental verification of antibacterial and antioxidant activity of 7-hydroxy-3-pyrazolyl-4H-chromen-4-ones and their o-glucosides: identification of pharmacophore sites

This paper reports the computational evaluation and experimental verification of 7-hydroxy-3-(1-phenyl-3-aryl-1H-pyrazol-5-yl)-4H-chromen-4-ones 3 and their o-β-d-glucopyranosides 5 for their antimicrobial and antioxidant activity. The prepared compounds were tested against various Gram-positive and Gram-negative bacteria species. Some of the synthesized compounds have shown potential antimicrobial and antioxidant activity. This POM bioinformatic study could greatly help to pharmacomodulate the potential antibiotics and antioxidants.Graphical AbstractThis paper describes the computational POM (Petra/Osiris/Molinspiration) evaluation and experimental verification of 7-o-β-d-glucopyranosyloxy-3-(1-phenyl-3-aryl-1H-pyrazol-5-yl)-4H-chromen-4-ones and metabolites for their antimicrobial and antioxidant activity.

Outstanding effect of the conformational restriction of isoquinolines: hints for the development of optimized antimicrobial agents

Conformational restriction constitutes a useful strategy of molecular modification for the design of new potential drug candidates. Herein we present the planning, antimicrobial evaluation, and establishment of structure–activity relationship (SAR) data for some isoxazole (3a–k, 8a–c, and 9a–c) and pyrazole (5a–h) derivatives. These derivatives were structurally designed by conformational restriction followed by bioisosteric exchange of previously described antimicrobial isoquinolines (1a–c). Some of these more conformationally restricted derivatives present improved properties as new antibacterial drug candidates.

POM as a quick bioinformatic platform to select flavonoids and their metabolites as potential and efficient HIV-1 integrase inhibitors

This paper surveys the various naturally occurring flavonoids that have been isolated from different natural sources. This is the first petra/osiris/molinspiration (POM) analysis published on this topic. The present study furnishes an overview of the 32 flavonoids and anti-HIV-Integrase activity of their metabolite species. The aqueous and/or ethanol extraction of flavonoids have often been used in traditional medicine, and therefore have also been studied for their antitumor, antioxidant, antiviral, anti-algal, antimicrobial, cytotoxic and anti-inflammatory, and significant hepatoprotective and cardiovascular activity without any criteria of selection. Here, on the basis of POM analyses, a simple, economic, quick and efficient bioinformatic platform, it now becomes easy and possible to predict and optimize flavonoids bioactivity.Graphical Abstract

Novel oxazine skeletons as potential antiplasmodial active ingredients: Synthesis, in vitro and in vivo biology of some oxazine entities produced via cyclization of novel chalcone intermediates

A novel series of 6-(2-chloroquinolin-3-yl)-4-substituted-phenyl-6H-1,3-oxazin-2-amines were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive (MRC-02) as well as chloroquine resistant (RKL9) strains of Plasmodium falciparum. The activity tested was at nanomolar concentration. β-Hematin formation inhibition activity (BHIA50) of oxazines were determined and correlated with antimalarial activity. A reasonably good correlation (r = 0.49 and 0.51, respectively) was observed between antimalarial activity (IC50) and BHIA50. This suggests that antimalarial mode of action of these compounds seems to be similar to that of chloroquine and involves the inhibition of hemozoin formation. Some of the compounds were showing better antimalarial activity than chloroquine against resistant strain of P. falciparum and were also found to be active in the in vivo experiment.

Antimicrobial/antioxidant activity and POM analyses of novel 7-o-β-d-glucopyranosyloxy-3-(4,5-disubstituted imidazol-2-yl)-4H-chromen-4-ones

A series of 7-o-β-d-glucopyranosyloxy-3-(4,5-disubstituted imidazol-2-yl)-4H-chromen-4-ones 4 were synthesized and tested for in vitro antibacterial/antifungal and antioxidant activity. The synthesized compounds o-β-d-glucoside of 7-hydroxyl-3-imidazolyl-4H-chromen-4-ones showed good antibacterial/antifungal activity as well as antioxidant activity. The results suggest that aglycone as well as their o-glucosides could be promising candidates for new combined antifungal/antibacterial as well as antioxidant agents (3 in 1). Experimental data and Petra/Osiris/Molinspiration (POM) analyses, respectively, show high bioactivity against various microorganisms at a very low concentration without any side effect, suggesting that series 2–4 is a potential antimicrobial inhibitor and further it deserves to be validated for in vivo studies.Graphical Abstract7-Hydroxy-3-(4,5-disubstituted imidazol-2-yl)-4H-chromen-4-ones and their o-β-d-glucosides were synthesized and evaluated for in vitro antimicrobial and antioxidant activity. The compounds were also subjected to high-throughput POM bioinformatics to study the bioavailability.

Synthesis, biopharmaceutical characterization, and antimicrobial study of novel azo dyes of 7-hydroxy-4-methylcoumarin

Herein, we report the synthesis and biopharmaceutical characterization of coumarin based azo compounds. The novel coumarin based azo compounds were obtained by the coupling of bis-coumarin (2Z,2′Z)-2,2′-[ethane-1,2-diylbis(azan-1-yl-1-ylidene)]bis(4-methylchroman-7-ol) with diazotized aromatic amines. The compounds were fully characterized using spectroscopic analytical method and tested for their antibacterial and antifungal activity. A correlation of structure and activities relationship of these compounds with respect to molecular modeling, Lipinski rule of five, drug-likeness, toxicity profiles, and other physico-chemical properties of drugs are described and verified experimentally.