SYNTHESIS AND ANTI-TUMOR ACTIVITY OF 4-DEMETHOXYADRIAMYCIN AND 4-DEMETHOXY-4'-EPIADRIAMYCIN

Abstract

Two new analogs of adriamycin were obtained by chemical synthesis, 4-demethoxyadriamycin and 4-demethoxy-4''-epiadriamycin. Both compounds were highly effective against experimental mouse tumors at doses about 10 times lower than those effective for adriamycin. At the optimal dose, 4-demethoxyadriamycin displayed antitumor activity similar to that of adriamycin in solid sarcoma 180 (S180), L1210, P388 and Gross leukemias and mammary carcinoma, while it did not markedly inhibit the growth of Moloney sarcoma virus-induced sarcoma in mice treated before the virus infection. At the optimal dose, 4-demethoxy-4''-epiadriamycin was as active as adriamycin against L1210, P388 and Gross leukemias, and less active against solid S180. The results show that anthracycline derivatives characterized by the absence of the methoxyl group at the C-4 position are more potent than the parent compound, and may exhibit a differential antitumor effect on a number of mouse tumors.