Synthesis and biological evaluation of combretastatin analogs as cell cycle inhibitors of the G1 to S transition in Saccharomyces cerevisiae

A series of Z and E combretastatin A-4 analogs bearing different substituents (OH, F, NO2, NH2, B(OH)2) in the 3′ position were synthesized. These derivatives and Z and E combretastatin A-1 were analysed by monitoring their ability to inhibit cell growth in Saccharomyces cerevisiae. Combretastatin A-1 (2a), A-4 (2b) and compound 2c were found to inhibit yeast growth. Moreover, combretatstatin A-4 (2b) and compound 2c induced a G1 arrest by affecting the synthesis of Clb5 protein, the principal S-phase cyclin. The G1 arrest is coincident with the activation of the stress activated kinase Snf1.

Graphical abstractTo enlighten new anti-tumor activities, a series of combretastatin A-4 derivatives and combretastatin A-1 were prepared and evaluated in arresting yeast growth. The G1 arrest induced by some of these compounds was characterized by the down-regulation of G1 cyclin Clb5 and activation of the stress activated kinase Snf1.Figure optionsDownload full-size imageDownload as PowerPoint slide