Seema BhatnagarAmity Institute of Biotechlogy · Amity University
16.35· Ph.D (Chemistry)
Research Items (22)
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.
Estrogen receptor (ER) has been a therapeutic target to treat ER positive breast cancer, most notably by agents known as selective estrogen receptor modulators (SERMs). However, resistance and severe adverse effects of known drugs gave impetus to the search for newer agents with better therapeutic profile. ERα and ERβ are two isoforms sharing 56% identity, and having different physiological functions and expressions in various tissues. Only two residues differ in the active sites of the two isoforms motivating us to design isoform selective ligands. Guided by computational docking and molecular dynamics simulations, we have designed, synthesized and tested, substituted biphenyl-2,6-diethanones and their derivatives as potential agents targeting ERα. Four of the molecules synthesized exhibited preferential cytotoxicity in ERα+ cell line (MCF-7) compared to ERβ+ cell line (MDA-MB-231). Molecular dynamics (MD) in combination with molecular mechanics-generalized born surface area (MM-GBSA) methods could account for binding selectivity. Further co-treatment and E-screen studies with known ER ligands- estradiol (E2) and tamoxifen (Tam) indicated isoform selective anti-estrogenicity in ERα+ cell line which might be ER mediated. ERα siRNA silencing experiments further confirmed the ER selective nature of ligands.
- Jan 2016
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.
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 IC50value 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. © 2015, International Journal of Pharmacy and Pharmaceutical Science. All rights reserved.
- Jan 2015
Excessive accumulation of free radicals results in cellular oxidative damage which has been reported to initiate the progression of several diseases such as cancer, alzheimer’s disease and parkinson’s disease. Antioxidants are free radical scavengers that play an important role in preventing oxidative cell damage and repairing the damage caused by free radicals. Biphenyls have been reported as a promising free radical scavenging scaffold. The objective of the present study was to evaluate the antioxidant activity of biphenyl-2,6-diethanone derivatives. A series of biphenyl derivatives were synthesized by the reported procedures. The antioxidant activity of these derivatives was evaluated using DPPH and lipid peroxidation assay. The in vitro antioxidant studies indicated that substituted biphenyl-2,6- diethanones, 1(a-i) exhibited significant free radical scavenging activity. Compounds 1e exhibited maximum antioxidant potential with an IC50 value of 54.96μg/ml. The present investigation indicated that derivatives containing hydroxyl, amine and methoxy groups on the biphenyl-2,6-diethanone scaffold exhibited significant antioxidant activity.
- Feb 2012
Myristica fragrans HOUTT has been traditionally used by Asian Indians to treat stomach pains, dysentery, vomiting and the symptoms of malaria. It is also chewed to prevent foul breath. The present study was carried out to elucidate the antifungal effect of four extracts; hexane, chloroform, methanolic and ethanolic extract obtained from Mace. The extracts were concentrated and re-suspended in DMSO. MIC 80 was calculated by micro broth dilution method. Results have revealed the extracts to have good antifungal activity against Aspergillus niger and methanol and hexane extracts have been found to be most effective. Methanol and hexane extracts were also associated with de-melanization of Aspergillus niger. Further analysis revealed difference in the structure of the hyphal cell wall of methane and hexane extract treated cells.
- Jan 2012
Mace which is the aril of the fruit of Myristica fragrans HOUTT. Asian Indians have traditionally treated stomach pains, dysentery, vomiting, and the symptoms of malaria with mace. It is also chewed to prevent foul breath. The present study was carried out to elucidate the anti fungal effect of 4 extracts; Hexane, Chloroform, methanolic and Ethanolic extract obtained from Mace. The extracts were concentrated and re-suspended in ethanol. Their in-vitro susceptibility test was done by disc diffusion method. MIC80 was calculated by micro broth dilution method. Results have revealed the extracts to have good activity against both the fungal strain. Methanol and Hexane extracts have been found to be most effective against the organisms tested The MIC80 was found to be the least for Methanol extract 0.237 mg/ml against Candida albicans and 0.232 mg/ml for Aspergillus niger. Phytochemical analysis of the extracts has been conducted to ascertain the active principle associated with the antifungal activity.
- Jul 2011
A simple one-step method for the stereoselective synthesis of the compounds (II) and (III) without the use of a catalyst is presented.
- Dec 2010
A simple one-step synthetic methodology for stereoselective synthesis of E- and Z-3-bromo-2-vinyl chromones in quantitative yield in polar solvents under ambient conditions without the use of catalysts is reported.
The search for small molecules that preferentially target the functionally important surfaces of estrogen receptor and disrupt the transcriptional activity in the cell has emerged as a promising area towards rationale based drug design. Herein, we report substituted styryl chromones as a new class of compounds that exhibit selectivity for ERbeta binding at the second binding site of HT and antiproliferative activity in human breast cancer cell line.
- Sep 2001
In continuation of an ongoing program on developing nonsteroidal pregnancy interceptives to be used as a menses regulating agent, a new class of compounds belonging to 3-substituted amino-1-aryl-6-hydroxy-hex-2-ene-1-ones series has been investigated for pregnancy interceptive activity in the hamster and rat. The compounds were administered (subcutaneous) on days 4–8 (hamster) and 5–9 (rat) post coitum (PC). The animals were laparotomized on days 12 (hamster) and 16 (rat) PC. To derive percent efficacy, the total number of implantation was divided by the number of normal and resorbed implantations. Among the 14 compounds evaluated, three were found to intercept pregnancy by 100%. Another compound was active by 75%, whereas the rest were inactive. None of the active compounds were, however, active in rat with this schedule. Results indicate that the observed species- and schedule-specific activity owes its origins to differences in the implantation physiology and early post-implantation development between the two species. The study, nevertheless, offers an insight to the new class of compounds for this activity.
- Sep 2000
A new series of compounds belonging to 3-substituted amino-1-aryl-6-hydroxy-hex-2-ene-1-ones (4-12a-e) have been synthesized and evaluated for antioxidant and hypolipidemic activities. Amongst all the synthesized compounds, seven compounds, namely 5b, 5d, 6e, 8a, 8b, 10b and 11a, exhibit better antioxidant activity than probucol. Two compounds, 5d and 10b, have been evaluated in detail for antioxidant and hypolipidemic activities and show comparable activity profile to that of probucol and guggulipid. From the present study it may be postulated that the mechanism of action of these compounds could be through activation of lecithin cholesterol acyltransferase (LCAT), liver lipolytic activity, increased faecal bile acid secretion and inhibition of hepatic cholesterol biosynthesis.
- Jan 2000
A new series of compounds belonging to 3-substituted amino-1-aryl-6-hydroxy-hex-2-ene-1-ones (4–12a–e) have been synthesized and evaluated for antioxidant and hypolipidemic activities. Amongst all the synthesized compounds, seven compounds, namely 5b, 5d, 6e, 8a, 8b, 10b and 11a, exhibit better antioxidant activity than probucol. Two compounds, 5d and 10b, have been evaluated in detail for antioxidant and hypolipidemic activities and show comparable activity profile to that of probucol and guggulipid. From the present study it may be postulated that the mechanism of action of these compounds could be through activation of lecithin cholesterol acyltransferase (LCAT), liver lipolytic activity, increased faecal bile acid secretion and inhibition of hepatic cholesterol biosynthesis.
- Dec 1999
Several compounds belonging to 2-isoxazolines (4,5a-c), isoxazoles (3,6a-c) and 1-amino-1-cycloalkyl-2-substituted phenyl ethanes (16-18,a-e) have been synthesised and found to possess spermicidal activity. Out of these a couple of compounds (5a and 6a) exhibit anti-HIV activity.
- Jun 1996
An acid catalysed ring transformation of 5-acyl/ alkoxycarbonyl - 2 - amino - 4 -aryl-3-cyano-6-methyl-4H-pyrans (1-3) to give 5-acyl/alkoxycarbonyl-4-aryl-3-cyano-1,2,3,4-tetrahydropyridin-2-ones (5-7) in the presence of formic acid has been carried out. The first report on a facile acid catalysed novel rearrangement of 2-amino-4-aryl-3-cyano-4H-naphtho[1,2-b]pyrans (4a-c) to 4-aryl-3-cyano-3,4-dihydronaphtho[1,2-b]-pyran-2(H)-ones (8a-c) under similar conditions is also described.