Top: Structures of representative compounds.Bottom: Antitubulin and antiproliferative activities of representative compounds.(Image by SIMM)

Anti-tubulin agents are widely used in clinic for the therapy of solid tumors. However, the toxicity and intrinsic or acquired resistances limit their clinical efficacy. Therefore, the search for novel anti-tubulin agents with higher efficacy and lower toxicity is of significant importance.

Through the tight collaboration between LOU Liguang’s group and HU Youhong’s group at Shanghai Institute of Materia Medica, CAS,a novel series of 2,4,5-substituted pyrimidine derivatives have been designed, synthesized and evaluated for their biological activity. These pyrimidine derivatives inhibit purified tubulin polymerization through binding to tubulin at the colchicine-binding site, induce G2/M cell-cycle arrest and inhibit human tumor cell proliferation. Some indole-pyrimidine compounds may have great potential for further development as anticancer therapeutics.

This work was supported by National Science & Technology Major Project“Key New Drug Creation and Manufacturing Program”and the National Natural Science Foundation of China. This work has been published in the Journal of Medicinal Chemistry (2011, 54：2127-2142)

Full text: http://pubs.acs.org/doi/abs/10.1021/jm101388d