SYNTHESIS OF 1,2-AZOLE DERIVATIVES ON THE BASIS OF α,β-UNSATURATED TRITERPENE ALDEHYDES

Abstract

α,β-Unsaturated lupane and 19β,28-epoxy-18α-oleanane aldehydes were used in the synthesis of triterpenoids bearing substituted 1,2-azole moieties (1-acetyl-3-methyl-4,5-dihydro-1H-pyrazole and 3-methyl-4,5-dihydroisoxazole) at the rings А and Е. The route of synthesis for these 1,2-azole derivatives of triterpenes included an aldol condensation of α,β-unsaturated aldehydes with acetone, the products of which (α,β-unsaturated methyl ketone and β-hydroxy ketone) underwent a further cycloaddition reaction with acetylhydrazide and hydroxylamine. Cytotoxic activity studies of the synthesized compounds against seven cancer cell lines (Hep-2, HCT116, MS, RD TE32, A549, MCF-7, and PC-3) showed that the highest cytotoxicity (IC50 0.66–11.97 μM) against all tested cell lines was exihbited by 19β,28-epoxy-18α-oleanane aldehyde and the products of its condensation reactions with acetone and acetylhydrazide.