NEIHUMICIN, A NEW CYTOTOXIC ANTIBIOTIC FROM MICROMONOSPORA NEIHUENSIS

III. STRUCTURE-ACTIVITY RELATIONSHIPS

Abstract

Structure-cytotoxicity relationships studies have indicated that the C-3 and C-6 disubstituted piperazine-2, 5-diones are structurally required for significant cytotoxicity, and the neihumicin-like C-3 and C-6 disubstituted unsymmetrical piperazine derivatives are, in general, more cytotoxic than the corresponding symmetrical piperazine-2, 5-diones. Several synthetic analogs including 3, 6-di-(2, 4, 5-trimethoxybenzylidene)piperazine-2, 5-dione, 3, 6-dibenzylidene-2-ethoxy-3, 6 -dihydropyrazine-5- one, 3-benzylidene-6-(m-chlorobenzylidene)-2-methoxy-3, 6-dihydropyrazin-5-one, and 3, 6-di-(m-chlorobenzylidene)-2-methoxy-3, 6-dihydropyrazin-5-one, have been shown to be more cytotoxic than neihumicin.