DOCKING AND CYTOTOXICITY STUDIES OF 2-VINYLCHROMONE DERIVATIVES ON HUMAN BREAST CANCER CELL LINES

Objective: Estrogen receptor (ER) is over-expressed in 70% of breast cancers. The ER has two isoforms, ERα and ERβ. The ER ligand binding domain (LBD) has been the target for hormone-responsive breast cancer. Due to tissue-specific effects currently available drugs for hormone positive breast cancer presents serious limitation. The dynamic and plastic nature of ER LBD plays a crucial role in ligand design that discriminates between the ER subtypes. Agents that selectively target ER isoform are a formidable challenge to researchers. The chromone scaffold is a privileged scaffold for exploration of anticancer agents. The objective of the present study was to evaluate the anticancer activity of a small library of 2-vinylchromones in human breast cancer cell lines MCF-7 and MDA-MB-231.Methods: The compounds were synthesized by the reported procedures. Docking studies of the substituted 2-vinylchromone was performed using GLIDE tool in Maestro 8.0. The compounds were evaluated for anticancer activity against MCF-7 (ERα positive), MDA-MB-231 (ERβ positive) and MRC-5 (ERα, β negative) cell lines using MTT assay.Results: The in silico studies indicated that substituted 2-vinylchromones, 1(a-c) and 2(a-b) exhibited comparable docking score at LBD of ERα and ERβ. However, the binding affinity of the compounds for the allosteric binding site in ERβ was negligible. The dose-dependent studies using MTT assay depicted that compounds 1(a-c) and 2(a-b) exhibited anticancer activity in ERα positive cell line MCF-7 as compared to ERβ positive cell line MDA MB 231. The most potent anticancer activity was observed for compound 2b against MCF-7 cells with IC50 value of 15.625 μg/ml.Conclusion: The present investigation indicated that 2-vinylchromone derivatives exhibited ER isoform selectivity and the presence of bulky group in 2-vinylchromones resulted in significantly higher cytotoxicity in ERα positive cell lines as compared to the ERβ positive cell line.Â

ANTIFUNGAL ACTIVITY OF BIPHENYL-2,6-DIETHANONE DERIVATIVES

Objective: The objective of the study was to evaluate the antifungal activity of biphenyl-2,6-diethanone derivatives against Cryptococcus neoformans.Methods: Antifungal activity of biphenyl derivatives were evaluated against C. neoformans. Zone of inhibition by disc diffusion method and minimum inhibitory concentration (MIC) using micro-broth dilution method was performed as per clinical and laboratory standard institute (CLSI). Melanin was extracted using 1M KOH, purified using 6M HCL and its reduction was assayed spectrophotometrically at 530 nm. Laccase activity was measured using L-DOPA as substrate and was assayed spectrophotometrically at 480 nm. Time kill assay was also performed to compare the antifungal potency of the test compound against azole drug.Results: Zone of inhibition of 12 mm diameter was estimated against C. neoformans. MIC80 of compound 1e was calculated as 50µg/ml. 63.67% decrease in melanization and 57.44% laccase activity reduction was determined. The Time-kill assay illustrated that the compound 1e inhibited the growth of C. neoformans cells in almost the same duration as observed in fluconazole.Conclusion: The outcome of in vitro antifungal studies indicated that compound 1e demonstrated maximum reduction of melanin and laccase activity in C. neoformans. In conclusion, biphenyl-2,6-diethanone derivatives possess significant antifungal property which can be explored further for lead generation.Â

ANTIBIOGRAM PROFILING OF HELICOBACTER PYLORI STRAINS AND THE EFFICACY OF BRASSICA CAPITATA AGAINST RESISTANT STRAINS ISOLATED FROM THE PATIENTS SUFFERING FROM GASTRODUODENAL DISEASES IN GUWAHATI, ASSAM

  Objective: Helicobacter pylori resistance toward commonly used antibiotics is increasing leading to the treatment failure; hence, our aim is to determine the antibiogram susceptibility pattern of H. pylori strains isolated from Guwahati, Assam (Northeast India) and also to test the efficacy of the Brassica capitata against the multi and dual drug-resistant strains of North and Northeast India.Methods: Minimum inhibitory concentration of different antibiotics was determined by agar dilution method. Disc diffusion method was used to check the efficacy of B. capitata against clarithromycin (CLR), metronidazole (MTZ), and levofloxacin (LEV)-resistant H. pylori strains.Results: All the H. pylori strains were 100% sensitive to CLR, tetracycline, amoxicillin, and furazolidone. 72.8% of the strains were sensitive toward MTZ and 54.5% were sensitive toward LEV. B. capitata showed good efficacy against the resistant strains of H. pylori of North and Northeast India.Conclusion: Most of the H. pylori strains from Northeast India were sensitive toward the commonly used antibiotics for the treatment regime. B. capitata is effective against H. pylori infection, suggesting its potential as an alternative therapy, and opens the way for further studies on identification of novel antimicrobial targets of B. capitata