Synthesis, transformation and biological evaluation of 2,3-secotriterpene acetylhydrazones and their derivatives
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- 作者：Victoria V. Grishko ; Irina A. Tolmacheva ; Natalia V. Galaiko ; Anastasia V. Pereslavceva ; Lada V. Anikina ; Larisa V. Volkova ; Boris A. Bachmetyev ; Pavel A. Slepukhin
- 关键词：A-secotriterpenoids ; Betulin ; 18¦Â-Glycyrrhetinic acid ; Antiviral activity ; Cytotoxicity ; Apoptosis
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：68
- 期：Complete
- 页码：203-211
- 全文大小：1293 K
文摘
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-19¦Â,28-epoxy-18¦ÁH-olean-3-al (<strong class=""boldFont"">1strong>, <strong class=""boldFont"">2strong>) inhibit the vesicular stomatitis virus (VSV) replication. To improve the antiviral activity against VSV, structural modifications of compounds <strong class=""boldFont"">1strong> and <strong class=""boldFont"">2strong> were performed, and new A-secoderivatives containing the acetylhydrazone fragment were obtained from betulonic acid and its methyl ester, allobetulone, and 3-oxo-18¦ÂH-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¡ä-acetyl-5¡ä-methyl-1¡ä,3¡ä,4¡ä-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 <strong class=""boldFont"">11astrong>. The pro-apoptotic effect of <strong class=""boldFont"">11astrong> was confirmed by the AnnexinV/PI analysis.