Synthesis of Novel Bioactive Compounds Akin to Combretastatin
Sunil Kumar
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab-142001, India
Abstract:
Combretastatin is a small organic molecule found in the bark of African bush willow tree Combretum caffrum, identified 21 year ago by Professor George R. Petit, the Director of the Cancer Research Institute based at Arizona State University in the USA. It is stated about CAP4 that it is the most cytotoxic phytoconstituent isolated so far. The present work involves synthesis of pharmacodynamics in general, combretastatin analogues in particular having free carboxylic function at the bridge head part of the target compounds. This substitution is expected to have restricted rotation and thus enhance desired anticancer activity of the synthesized compounds. The highlight of the present work involves replacement of one of the phenyl ring of the combretastatin with the indole ring because presence of such moiety provides necessary electron cloud towards periphery of ring A of combretastatin (butterfly model) besides indole alkaloids viz., vincristine, vinblastine, elliptinium, and bromoindirubin are known to be potent anticancer compounds. As such 12 combretastatin analogues (1-12) have been synthesized by condensation process. Out of these compounds, 5 and 12 showed potent anticancer activity against THP-I(leukemia), A-549(lung)and MCF-7(breast)cancer cell lines.
