Preparation of novel ring-A fused azole derivatives of betulin and evaluation of their cytotoxicity.

An efficient scheme to synthesize novel ring-A fused heterocyclic derivatives of betulin was developed. The starting reaction of this synthesis was one-pot selective bacterial oxidation of betulin to betulone used as the key compound to synthesize the substituted azoles such as C(2)-C(3)-fused 1,2,3-triazoles, oxazoles and 1,2,4-triazine, as well as C(1)-C(2)-fused isoxazoles. The semi-synthetic compounds were screened for their cytotoxic activity against human cancer cell lines A549, HCT 116, HEp-2, MS and RD TE32 with use of the photometric MTT assays.

Functionalization, cyclization and antiviral activity of A-secotriterpenoids.

Triterpene derivatives with an α,β-alkenenitrile moiety in the five-membered ring A have been synthesized by nitrile anion cyclizations of 1-cyano-2,3-secotriterpenoids. Oxime-containing precursors, 2,3-secointermediates and five-membered ring A products of cyclizations were screened for in vitro antiviral activity against enveloped viruses - influenza A virus and human immunodeficiency virus type I (HIV-1). Lupane ketoxime and the 2,3-secolupane C-3 aldoxime which possess antiviral activities against both influenza A virus (EC50 12.

Synthesis, transformation and biological evaluation of 2,3-secotriterpene acetylhydrazones and their derivatives.

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.

[Antiviral activity of 2,3-secotriterpenic hydrazones of lupane and 19beta,28-epoxy-18alpha-oleanane type].

Novel hydrazones of lupane and 19beta,28-epoxy-18alpha-oleanane type have been synthesized via interaction of 2,3-secotriterpenic aldehydonitriles with substituted hydrazines. As a result of investigation of 2,3-secotriterpenic hydrazones antiviral activity to the strain "Indiana" of vesicular stomatitis virus on two models of mammal's line cell infection, acetylhydrazone 1-cyano-2,3-seco-19beta,28-epoxy-18alpha-olean-3-al has been found to have a high prophylactic activity 0.00016 microg/ml to vesicular stomatitis virus and to inhibit a virus reproduction in primarily infected cells in 0.