Design, Synthesis, In-Silicostudies, and Screening of Novel Chalcones and Their Pyrazoline Derivatives against Mycobacterium Tuberculosis

A new series of naphthyl chalcones (II 3a-3p) and their pyrazoline derivatives(II 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 anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27924) and anti-bacterial activity against Staphylococcus aureus (MTCC 96), Bacillus subtilis (MTCC 441), Escherichia coli (MTCC 443)and Klebsiella pneumonia (MTCC 109). Amongst the synthesized compounds,compound- II-4bwith2-hydroxy-5-bromophenyl substitution at 3rd position of pyrazoline showed significant antimycobacterial activity with MIC of 6.25µM comparable to that of standard isoniazid. Compounds 3band 3p exhibited significant antibacterial activity against all the tested bacterial strains. 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& 4hdid notexhibit anycytotoxicity, andother compounds showed IC50 values higher than 8 & 22 µM against MDA-MB-231 and SKOV3 cell lines respectively compared to 1.20 & 1.30 µM shown by standard doxorubicin. In order 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-II-4b, displayed ahydrogen bond interaction with docking score of -10.50 kcal/mol and energy of-44.50 kcal/mol, weakly active compound-II-3h did not show any crucial hydrogen bond interaction with the surrounded amino-acid residues and revealed a docking score of -6.74 kcal/mol and docking energy of -42.50 kcal/mol.