Cancer, an unrestrained proliferation of cells, is one of the lead cause of death. Nearly 12.5 million people are diagnosed with cancer worldwide, 7.5 million people die of which 2.5 million cases are from India. Major cause for cancer is restriction of programmed cell death (apoptosis). Multiple signaling pathways regulate apoptosis. Bcl-2 (B - Cell Lymphomas-2) family proteins play a vital role as central regulators of apoptosis. Bcl-2L10, a novel anti-apoptotic protein, blocks apoptosis by mitochondrial dependent mechanism. The present study evaluates the 3D structure of Bcl-2L10 protein using homology modeling and aims to understand plausible functional and binding interactions between Bcl-2L10 with BH3 domain of BAX using protein - protein docking. The docking studies show binding of BH3 domain at Lys 110, Trp-111, Pro-115, Glu-119 and Asp-127 in the groove of BH 1, 2 and 3 domains of Bcl-2L10. Heterodimerization of anti-apoptotic Bcl-2 and BH3 domain of pro-apoptotic Bcl-2 proteins instigates apoptosis. Profound understanding of Bcl-2 pathway may prove useful in identification of future therapeutic targets for cancer.
A series of 36 novel substituted quinazolinone derivatives were synthesized and evaluated for their antiinflammatory activity by carrageenan induced paw inflammation model. The ability of these compounds to inhibit cyclooxygenase (COX-1 and 2) enzyme has been determined in-vitro; the results indicated that quinazolinone derivatives were selective towards COX-2 rather than COX-1. Among the quinazolinone derivatives tested, compound 32 showed better inhibition against COX-2 when compared with Celecoxib. Pharmacophore modeling and 3D QSAR studies were performed in order to elucidate structural insights for the anti-inflammatory activity.
A series of novel substituted 8-bromo-2-(dimethylamino)-3-(3-(dimethylamino) propyl) quinazoline-4(3H)-one derivatives 2(a-h) were prepared with excellent yields and evaluate their antimicrobial activity. These compounds 2(a-h) are prepared the by the reactions between 8-bromo-3-(2-(dimethylamino) ethyl)-2-(methylthio) quinazoline-4(3H)-one and secondary amines. These all compounds characterization done by different spectroscopic methods PMR, IR, CMR, Mass Spectral and elemental data. All compounds were evaluated for their biological activity i.e., antibacterial and anti-fungal activity. The anti-bacterial activities were evaluated in vitro method. The antibacterial activity 8-bromo-2-(dimethylamino)-3-(3-(dimethylamino) propyl) quinazoline-4(3H)-one derivatives 2(a-h) was assessed against three representative Gram-positive bacteria viz. Bacillus subtilis, Bacillus sphaericus and Staphylococcus aureus, and three Gram-negative bacteria viz. Pseudomonas aeruginosa, Klebsiella aerogenes and Chromobacterium violaceum, and antifungal activity against Candida albicans, Aspergillus fumigates, Trichophyton rubrum and Trichophyton mentagrophytes. Among all these compounds most of the compounds were exhibit more potent anti-bacterial and anti-fungal activity against standard drugs.
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