BITS Faculty Publications
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Item Design, synthesis, in silico studies, and evaluation of novel chalcones and their pyrazoline derivatives for antibacterial and antitubercular activities(Springer, 2020-07) Murugesan, SankaranarayananA new series of naphthyl chalcones (3a–3p) and their pyrazoline derivatives (4a–4h) were synthesized using substituted acetophenones, substituted naphthaldehydes, and hydrazine hydrate as starting materials. All the synthesized compounds were characterized by IR, NMR, and mass spectrometric analysis and screened for antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27924) and antibacterial activity against Staphylococcus aureus (MTCC 96), Bacillus subtilis (MTCC 441), Escherichia coli (MTCC 443) and Klebsiella pneumonia (MTCC 109). Compounds 3b and 3p exhibited significant antibacterial activity against all the tested bacterial strains. Amongst the synthesized compounds, compound 4b with 2-hydroxy-5-bromophenyl substitution at 3rd position of pyrazoline showed significant antimycobacterial activity with MIC of 6.25 µM comparable to that of standard isoniazid. The synthesized compounds were further screened for their cytotoxic activity against the MDA-MB-231 and SKOV3 cell lines. The compounds 3a, 3l, 4b, 4c, 4e, and 4h did not exhibit any cytotoxicity, and other compounds exhibited IC50 values higher than 8 and 22 µM against MDA-MB-231 and SKOV3 cell lines, respectively, compared to 1.20 and 1.30 µM shown by standard doxorubicin. To find out the putative binding mode of significantly active and weakly active compounds, a molecular docking study was also performed. In that, the most active compound 4b, displayed a hydrogen bond interaction with docking score of −10.50 kcal/mol and energy of −44.50 weakly active compound 3h did not show any crucial hydrogen bond interaction with the surrounded amino-acid residues and revealed a docking score of −6.74 and docking energy of −42.50.Item Synthesis, evaluation and molecular docking studies of amino acid derived N-glycoconjugates as antibacterial agents(Elsiever, 2015-12) Jha, Prabhat N.; Sah, Ajay Kumar; Murugesan, SankaranarayananSix amino acid derived N-glycoconjugates of d-glucose were synthesized, characterized and tested for antibacterial activity against G(+)ve (Bacillus cereus) as well as G(−)ve (Escherichia coli and Klebsiella pneumoniae) bacterial strains. All the tested compounds exhibited moderate to good antibacterial activity against these bacterial strains. The results were compared with the antibacterial activity of standard drug Chloramphenicol, where results of A5 (Tryptophan derived glycoconjugates) against E. coli and A4 (Isoleucine derived glycoconjugates) against K. pneumoniae bacterial strains are comparable with the standard drug molecule. In silico docking studies were also performed in order to understand the mode of action and binding interactions of these molecules. The docking studies revealed that, occupation of compound A5 at the ATP binding site of subunit GyrB (DNA gyrase, PDB ID: 3TTZ) via hydrophobic and hydrogen bonding interactions may be the reason for its significant in vitro antibacterial activity.Item Rational Design, Synthesis, Anti-HIV-1 RT and Anti-microbial Activity of Novel 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-phenylpropanamide Derivatives(Bentham Science, 2016) Jha, Prabhat N.; Murugesan, SankaranarayananBackground: AIDS continues to be a major public health issue worldwide. In 2014, an estimated 36.9 million people were living with HIV, in the same year, around 1.2 million people died due to AIDS-related illnesses. Due to global efforts particularly made in the last decade has reduced mortality rate due to AIDS and associated diseases. But still many people living with HIV/AIDS particularly in the low and middle income countries do not have access of anti-HIV drugs. Moreover, still there is no permanent cure of disease and rapid emergence of drug resistance by HIV towards the current available therapy further drive the need for the search of new potential anti- HIV drugs. Methods: In the present study, fifteen novel 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-phenylpropanamide derivatives (5a-o) were designed as HIV-1 Reverse Transcriptase (RT) inhibitors, in-silico evaluated for drug likeness behaviour, synthesized and characterized. Compounds were evaluated in-vitro for inhibition of HIV-1 RT activity. Three compounds (5a, 5f and 5o) as representative of the series were evaluated for cytotoxicity studies on human T lymphocytes (C8166 cells). All the synthesized compounds were also evaluated for in-vitro antibacterial (E. coli, P. putida, S. aureus and B. cereus) and antifungal (C. albicans and A. niger) activity. Results: All compounds (5a-o) possessed drug-likeness behavior based upon their in-silico predicted drug-likeness properties. Five compounds 5f, 5h, 5i, 5k and 5n exhibited more than 50% inhibition of HIV-1 RT, in which compound 5h showed highest inhibition (61%). Cytotoxicity studies of compounds 5a, 5f and 5o on T lymphocytes revealed that, all three exhibited CC50 >200 µg/ml. Four compounds 5f, 5i, 5j and 5n showed significant inhibition against the tested G(-) ve (E. coli and P. putida) bacterial strains while one compound 5f significantly inhibited the growth of all tested bacterial strains. Among the series, four compounds (5e, 5f, 5i and 5m) significantly inhibited the growth of A. niger, while compound 5m exhibited significant inhibition of both the tested fungal strains. Conclusion: Titled compounds (5a-o) exhibited weak to significant inhibition of HIV-1 RT, particularly 5h. Four compounds showed significant anti-bacterial activity against the both tested G(-)ve bacterial strains, moreover compound 5f significantly inhibited the growth of all four tested bacterial strains. Four compounds significantly inhibited the growth of A. niger, in which compound 5m exhibited significant inhibition of both the tested fungal strains.