title: 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)2Mg(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)2Mg(2+) dimers, whereas the O-acyl group in E-olivomicose residue largely participates in the formation of the (olivomycin)2Mg(2+)-DNA complexes.
authors.affiliation: Gause Institute of New Antibiotics, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Tevyashova
authors.forename: Nikita A
authors.initials: NA
authors.lastname: Durandin
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Vinogradov
authors.forename: Victor B
authors.initials: VB
authors.lastname: Zbarsky
authors.forename: Marina I
authors.initials: MI
authors.lastname: Reznikova
authors.forename: Lyubov G
authors.initials: LG
authors.lastname: Dezhenkova
authors.forename: Eugeniy E
authors.initials: EE
authors.lastname: Bykov
authors.forename: Eugenia N
authors.initials: EN
authors.lastname: Olsufyeva
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Kuzmin
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shtil
authors.forename: Maria N
authors.initials: MN
authors.lastname: Preobrazhenskaya
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry* / Q000494:pharmacology*; D002413:Cations, Divalent / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D009848:Olivomycins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D002241:Carbohydrates; D002413:Cations, Divalent; D004791:Enzyme Inhibitors; C025047:olivomycin A; D009848:Olivomycins; D004247:DNA; D004264:DNA Topoisomerases, Type I; D008274:Magnesium