Design, synthesis and biological evaluation of some novel benzothiazole/benzoxazole and/or benzimidazole derivatives incorporating a pyrazole scaffold as antiproliferative agents

[Display omitted] •A series of substituted pyrazoles10a-c, 11a-c and 12a- was designed and prepared.•All the candidates benzimidazolo/benzoxazolo/benzothiazolo-pyrazolone hybrids were evaluated in vitro for their antiproliferative activity.•Compound 12a was the most active compound against both MCF-7 and A549 cell lines.•Furthermore, the benzothiazole-pyrazolone derivative 13c was the most potent COX-2 inhibitor (IC50=0.10μM), while the 5-acetylbenzoxazolopyrazolone derivative 12a was the most COX-2 selective (S.I.=104.67) in comparison with celecoxib (COX-2 IC50=1.11μM, S.I.=13.33). In an aim at developing new antiproliferative agents, new series of benzothiazole/benzoxazole and/or benzimidazole substituted pyrazole derivatives 11a-c, 12a-c and 13a-c were prepared and evaluated for their antiproliferative activity against breast carcinoma (MCF-7) and non-small cell lung cancer (A549) cell lines. The target compound, 2-acetyl-4-[(3-(1H-benzimidazol-2-yl)-phenyl]-hydrazono-5-methyl-2,4-dihydropyrazol-3-one (12a) was the most active compound against both MCF-7 and A549 cell lines with half maximal inhibitory concentrations (IC50)=6.42 and 8.46μM, respectively. Furthermore, the inhibitory activity of the all the target compounds against COX enzymes was recorded as a proposed mechanism for their antiproliferative activity. The obtained results revealed that the benzothiazolopyrazolone derivative 13c was the most potent COX-2 inhibitor (IC50=0.10μM), while the 5-acetylbenzimidazolylpyrazolone derivative 12a was the most COX-2 selective (S.I.=104.67) in comparison with celecoxib (COX-2 IC50=1.11μM, S.I.=13.33). Docking simulation on the most active compounds 12a and 13c had been performed to investigate the binding interaction of these active compounds within the binding site of COX-2 enzyme.Collectively, this work demonstrated the promising activity of the newly designed compounds as leads for further development into antiproliferative agents.