Antitumor activity and cytotoxicity of a new ankinomycin derivative, 3'-,11-dibutyryl ankinomycin.

Ankinomycin is a new antitumor antibiotic found in the culture broth of Streptomyces sp. SF2587. Ankinomycin showed marked cytotoxicity and antitumor activity against some murine leukemias, but the activity against murine solid tumors was rather weak because of its strong acute toxicity. We synthesized ankinomycin acyl derivatives and examined their antitumor activity. Among the derivatives, 3',11-dibutyryl ankinomycin (AN1006) exhibited the highest antitumor activity. The antitumor activity of AN1006 was dependent on the administration schedule, and on the most effective schedule, AN1006 showed activity comparable with that of Adriamycin (ADM) against murine solid tumors and leukemias. AN1006 showed a cytotoxic spectrum different from that of ADM, exhibiting cytotoxicity stronger than that of ADM against colon carcinoma, stomach carcinoma, and some leukemia cell lines. According to these in vitro effects, AN1006 showed antitumor activity superior to and equal to that of ADM against human colon xenografts and stomach carcinoma xenografts in athymic nude mice, respectively. AN1006 was effective against multidrug-resistant tumors in vitro and in vivo. AN1006 is an interesting candidate for further evaluation.