Role of the acyl groups in carbohydrate chains in cytotoxic properties of olivomycin A.

A series of olivomycin A derivatives containing different combinations of the acyl residues in the carbohydrate chains was obtained. The formation of complexes of Mg(2+)-coordinated dimers of these compounds with double-stranded DNA was studied using spectral methods such as absorption, fluorescence and circular dichroism (CD) spectral analyses. There was a good correlation of the values of binding constants of complexes (antibiotic)2Mg(2+)-DNA, the quantum yields of fluorescence and changes of the induced CD spectra with topoisomerase I inhibition and cytotoxicity.

Modification of the antibiotic olivomycin I at the 2'-keto group of the side chain. Novel derivatives, antitumor and topoisomerase I-poisoning activity.

A novel way of chemical modification of the antibiotic olivomycin I at the 2'-keto group of the side chain of the aglycone moiety was developed. Reaction of olivomycin I with the carboxymethoxylamine hemihydrochloride gave the key intermediate, 2'-carboxymethoxime-olivomycin I, which was further reacted with different amines in the presence of benzotriazol-1-yl-oxy-trispyrrolidinophosphonium hexafluorophosphate to give the corresponding amides. The antiproliferative and topoisomerase I (Topo-I)-poisoning activities of the novel derivatives were examined.