Design, synthesis, in silico studies, and evaluation of novel chalcones and their pyrazoline derivatives for antibacterial and antitubercular activities

A 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 IC 50 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.