The development of small molecule modulators that interfere with microtubule dynamics through the interaction with the tubulin is a particularly valid approach in cancer chemotherapy. First, it was carried out a virtual screening with a series of substances synthesized from Morita-Baylis-Hillman adducts using three different types of program: GOLD, SURFLEX and AUTODOCK. After detailed evaluation of the complementary geometric 25 compounds were selected for biochemical assays. The cyclopenta<b>indole derivatives showed great potential of modulation of microtubule functions, with a significant decrease in the tubulin polymerization rate, a similar effect found for positive control colchicine. The molecular modeling suggested that the cyclopenta<b>indoles are held in colchicine-binding site by interaction of the indole nucleus with the side chain of ASN 249 and the hydroxyl group seems to be important to increasing activity and this data is in accordance with experimental assays.References INCA, Instituto Nacional de C�ncer, 2011.

Discovery of a novel class of tubulin polymerization inhibitors by virtual and biological screening

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.