Synthesis of Novel Tricyclic N-Acylhydrazones as Tubulin Polymerization Inhibitors.

A series of N-acylhydrazones bearing a 1,4-dihydroindeno[1,2-b]pyrrole ring, along with benzene and thiophene rings substituted with chlorine or methyl groups, was synthesized and evaluated for their antiproliferative and cytotoxic activity against the melanoma A375 cell line and to measure the inhibition of tubulin polymerization. Four compounds elicited interesting activity: derivatives, 1g and 1h showed a 25% slowdown of tubulin polymerization, whereas compounds 2c and 2d caused a slowdown of 40% and 60%, respectively. Molecular modelling results have confirmed that the most active N-acylhydrazones (1g, 1h, 2c, and 2d) may act as tubulin polymerization inhibitors.