Reaction of the antitumor antibiotic olivomycin I with aryl diazonium salts. Synthesis, cytotoxic and antiretroviral potency of 5-aryldiazenyl-6-O-deglycosyl derivatives of olivomycin I

Tevyashova, Anna N; Olsufyeva, Eugenia N; Turchin, Konstantin F; Balzarini, Jan; Bykov, Eugenyi E; Dezhenkova, Lyubov G; Shtil, Alexander A; Preobrazhenskaya, Maria N

doi:10.1016/j.bmc.2009.05.076

Reaction of the antitumor antibiotic olivomycin I with aryl diazonium salts. Synthesis, cytotoxic and antiretroviral potency of 5-aryldiazenyl-6-O-deglycosyl derivatives of olivomycin I

Author:

Tevyashova, Anna N

Olsufyeva, Eugenia N ; Turchin, Konstantin F ; Balzarini, Jan ; Bykov, Eugenyi E ; Dezhenkova, Lyubov G ; Shtil, Alexander A ; Preobrazhenskaya, Maria N

Keywords:

Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemistry & Molecular Biology, Chemistry, Medicinal, Chemistry, Organic, Pharmacology & Pharmacy, Chemistry, Olivomycin I, Arylazo coupling reaction, Antitumor antibiotic, Antiretroviral activity, SEMISYNTHETIC DERIVATIVES, GLYCOPEPTIDE ANTIBIOTICS, DNA-BINDING, BIOSYNTHESIS, MITHRAMYCIN, INHIBITION, COMPLEX, DRUG, Animals, Antibiotics, Antineoplastic, Borates, Boric Acids, Cell Line, Tumor, Cell Proliferation, Diazonium Compounds, Humans, Microbial Sensitivity Tests, Molecular Structure, Olivomycins, Viruses, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3101 Biochemistry and cell biology, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

The azo coupling of the antibiotic olivomycin I (1) with aryl diazonium tetrafluoroborates produced 5-aryldiazenyl-6-O-deglycosyl derivatives of 1. The structures of new compounds were confirmed by (1)H NMR and mass spectrometry analysis. A quantum-chemical study was performed to analyze the possible directions of electrophilic substitution of 1 and the easiness of 6-O-disaccharide hydrolysis in the course of azo coupling. The antiproliferative and anti-retroviral activities of novel derivatives were studied.