Modulation of microtubule network by ansamitocin P3, combretastatin analogues and centrosomal protein-centrobin

Microtubules are important anti-cancer drug targets. Several microtubule binding agents are clinically successful and are undergoing clinical trials for cancer chemotherapy. This thesis explores the regulation of microtubule network and anti-cancer activity by small molecules ansamitocin P3 and combretastatin analogues. The study provided a significant insight in understanding the anti-proliferative mechanism of action of ansamitocin P3. Further, cytotoxic and anti-tubulin activity of one of the potent combretastatin analogue was studied. In addition, the role of centrosomal protein-centrobin was examined. Centrobin depletion reduced the microtubule stability and induced spindle abnormalities. The results indicate that centrobin may be a promising anti-cancer target. Thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy of the Indian Institute of Technology Bombay, India and Monash University, Australia.