Design, Synthesis, Molecular Docking Studies, and Biological Evaluation of Pyrazoline Incorporated Isoxazole Derivatives

Abstract

A novel series of pyrazoline incorporated isoxazole derivatives were designed and synthesized. The synthesized compounds were characterized by 1H NMR, IR and ESI-MS spectra. In addition, all the synthesized compounds were docked with the target human DHFR (PDB ID: 1KMS). Among all the compounds, compound 5-(4-methoxyphenyl)-3-(5-methyl-3-(4-nitrophenyl)isoxazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)(phenyl)methanone proved to be the most potent exhibiting the highest binding affinity with a docking score of 153.763. All the synthesized compounds were screened for anticancer activity against human breast cancer cell lines MCF-7 and MDA-MB-231 through MTT assay. Out of all the synthesized compounds (5-(4-methoxyphenyl)-3-(5-methyl-3-(4-nitrophenyl)isoxazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)(phenyl)methanone posses good activity with IC50 values ranging from 3–4 μg/mL. Further all the compounds were screened for antitubercular assay against the strain H37Rv and multidrug resistant strain DKU 156, among all four compounds exhibited significant activity at 6.25 µg/mL concentrations. Thus the MIC value may be in between the range of 3.12 and 6.25 µg/mL.