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

  • Eur J Med Chem. 2014 Apr 9:76:460-9. doi: 10.1016/j.ejmech.2014.02.042.
G Saidachary  1 ,  K Veera Prasad  1 ,  D Divya  2 ,  Ashita Singh  2 ,  U Ramesh  2 ,  B Sridhar  3 ,  B China Raju  4
Affiliations
  • 1. Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
  • 2. Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
  • 3. Laboratory of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
  • 4. Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. Electronic address: [email protected].
PMID: 24607876 DOI: 10.1016/j.ejmech.2014.02.042
Abstract

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.

Keywords
Anti-mycobacterial activity; Anticancer activity; Benzoxepinoisoxazolones; Benzoxepinopyrazolones; Cyclocondensation.