Synthesis, cytotoxic evaluation, and molecular docking studies of the semi-synthetic “triterpenoid-steroid” hybrids

Publication date: Available online 11 October 2018Source: SteroidsAuthor(s): Irina A. Tolmacheva, Alexey V. Nazarov, Daria V. Eroshenko, Victoria V. GrishkoAbstractSynthetic transformations of steroids for drug discovery and improvement of drug effectiveness have been an important part of modern medicinal chemistry and pharmaceutical sciences. Pentacyclic triterpenoids, being represented in the nature by various structures and biogenetically related to steroids, can largely expand the spectrum of biologically active steroidal agents via synthesis of the so-called “triterpenoid-steroid” hybrids. In the presented work, the nitrile anion cyclizations of 3,4-secolupane and 3,4-seco-oleanane nitriles and follow-up synthetic transformations of the cyclized products with formation of the gemm-dimethyl-free A ring “triterpenoid-steroid” hybrids were studied. Furthermore, the resulting cyclic compounds were modified at C3, C4, and/or C5 positions of ring A, as well as at C20, C28, and C30 positions of the isopropylidene moiety in the case of lupane triterpenoids. The cytotoxic effect of the synthesized compounds against seven cancer cell lines HEp-2, HCT 116, MS, RD TE32, A549, MCF7, and PC3 was evaluated. The in silico identification of potential anticancer protein targets with regard to the compounds, which were active at micromolar concentrations against tested cell lines, was carried out. The molecular docking studies showed that compound 19, which demonstrated most pronou...

Source: Steroids - October 11, 2018 Category: Drugs & Pharmacology Source Type: research