Abstract
Active natural productscan be valuable lead compounds and numerous drugs derived from natural products have successfully entered the clinic. Arenobufagin, one of the important active components of toad venom, indicates significant antitumor activities with limited preclinical development for its strong cardiotoxicity. Ten 3-monopeptide substituted arenobufagin derivatives have been designed and synthesized. Antitumor activity and cardiotoxicity assays lead to the discovery of compound ZM226 as a potent antitumor agent with low cardiotoxicity. These findings suggest optimization of arenobufagin on position 3 maybe an efficacious strategy for the development of antitumor drug candidates derived from arenobufagin.
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