title: Synthesis, transformation and biological evaluation of 2,3-secotriterpene acetylhydrazones and their derivatives.
abstract: It has been previously shown that semi-synthetic A-secotriterpene acetylhydrazones of 1-cyano-28-methoxy-28-oxo-2,3-seco-2-norlup-20(29)-en-3-al and 1-cyano-2,3-seco-2-nor-19β,28-epoxy-18αH-olean-3-al (1, 2) inhibit the vesicular stomatitis virus (VSV) replication. To improve the antiviral activity against VSV, structural modifications of compounds 1 and 2 were performed, and new A-secoderivatives containing the acetylhydrazone fragment were obtained from betulonic acid and its methyl ester, allobetulone, and 3-oxo-18βH-glycyrrhetinic acid methyl ester. The inhibitory effects of these compounds on VSV replication in porcine embryo kidney (PEK) cells were determined after infection. It was shown that introduction of the 3'-acetyl-5'-methyl-1',3',4'-oxadiazoline fragment into lupane triterpene structures lead to an increase in the antiviral activity of A-secotriterpene derivatives. However, the presence of a heterocyclic moiety enhanced toxic activity and reduced the therapeutic indices of these agents. Investigation in the anti-proliferative activity of the heterocyclic derivatives has shown high sensitivity of A-549, MS and RD tumor cell lines to lupane (R)-oxadiazoline 11a. The pro-apoptotic effect of 11a was confirmed by the AnnexinV/PI analysis.
authors: Institute of Technical Chemistry, Ural Branch, Russian Academy of Sciences, 3, Akad. Korolev Str., 614013 Perm, Russia. Electronic address: grishko@aport.ru.
authors: Victoria V
authors: VV
authors: Grishko
authors: Irina A
authors: IA
authors: Tolmacheva
authors: Natalia V
authors: NV
authors: Galaiko
authors: Anastasia V
authors: AV
authors: Pereslavceva
authors: Lada V
authors: LV
authors: Anikina
authors: Larisa V
authors: LV
authors: Volkova
authors: Boris A
authors: BA
authors: Bachmetyev
authors: Pavel A
authors: PA
authors: Slepukhin
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D005434:Flow Cytometry; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013552:Swine; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018116:Vesiculovirus / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D006835:Hydrazones; D014315:Triterpenes
keywords: 18β-Glycyrrhetinic acid; A-secotriterpenoids; Antiviral activity; Apoptosis; Betulin; Cytotoxicity