Convenient one-pot synthesis, anti-mycobacterial and anticancer activities of novel benzoxepinoisoxazolones and pyrazolones

• Benzoxepinoisoxazolones and pyrazolones were designed as anti-mycobacterial and anticancer agents.
• Compounds 4d and 6b shown potent anti-mycobacterial activity.
• Compounds 4b–d shown potent cytotoxicity against cervical cancer (HeLa).
• Caspase-3 and caspase-9 activities were performed for compounds 4b–d on HeLa cell lines.

Series of new benzoxepinoisoxazolones 4a–d and pyrazolones 6a–t were prepared by the cyclocondensation of substituted (E)-ethyl 3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylates 3a–d with hydroxylamine hydrochloride and phenylhydrazine hydrochlorides 5a–k. Synthesized compounds were screened for their in vitro anti-mycobacterial activity and anticancer activity. Ten compounds displayed good anti-mycobacterial activity, among these; compound 4d and 6b found to be potent when compared to standard drug isoniazid. Eleven compounds displayed good anticancer activity and compounds 4b–d displayed equipotent activity on HeLa cell lines when compared to standard drug doxorubicin. Activation of caspase-3 and caspase-9 has been measured for compounds 4b–d on HeLa cell lines (apoptosis). This is the first report assigning in vitro anti-mycobacterial, anticancer and structure–activity relationship for this new class of benzoxepinoisoxazolones and pyrazolones.

Series of new benzoxepinoisoxazolones 4a–d, benzoxepinopyrazolones 6a–t were synthesized. Compounds 4d, 6b are potent anti-mycobacterial and serve as model compounds for design and development of therapeutic based agents.Figure optionsDownload as PowerPoint slide