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

Abstract

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) 2 Mg 2+ -DNA, the quantum yields of fluorescence and changes of the induced CD spectra with topoisomerase I inhibition and cytotoxicity. We demonstrate that the presence of the acyl groups in the saccharide residues of olivomycin A derivatives is absolutely necessary for a high cytotoxic potency of these antibiotics. On the basis of the experimental results and quantum chemical calculations, we presume that the acyl residue in the 4-O-position in the A-sugar residue is involved, to the most part, in the antibiotic-antibiotic interactions in the (olivomycin) 2 Mg 2+ dimers, whereas the O-acyl group in E-olivomicose residue largely participates in the formation of the (olivomycin) 2 Mg 2+ -DNA complexes. © 2013 Japan Antibiotics Research Association All rights reserved.