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. © 1988, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.