Title:Novel Hybrid Molecules on the Basis of Steroids and (5Z,9Z)-Tetradeca-5,9-dienoic Acid: Synthesis, Anti-Cancer Studies and Human Topoisomerase I Inhibitory Activity
VOLUME: 17 ISSUE: 8
Author(s):Vladimir A. D’yakonov*, Lilya U. Dzhemileva*, Regina A. Tuktarova, Svetlana R. Ishmukhametova, Milyausha M. Yunusbaeva, Ilfir R. Ramazanov and Usein M. Dzhemilev
Affiliation:Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075, Ufa, Department of Immunology and Human Reproductive Health, Bashkir State Medical University, 3 Lenin Street, 450003, Ufa, Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075, Ufa, Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075, Ufa, Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences 71 Prospect Oktyabrya, 450054, Ufa, Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075, Ufa, Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075, Ufa
Keywords:5Z, 9Z-Dienoic acids, steroids, cross-cyclomagnesiation, homogeneous catalysis, 1, 2-dienes, topoisomerase I inhibitors, cancer
cell lines, docking.
Abstract:Novel steroid derivatives of 5Z,9Z-dienoic acids were prepared by the DCC/DMAP-catalyzed
esterification of (5Z,9Z)-tetradeca-5,9-dienoic acid with hydroxy steroids. High cytotoxicity towards the HEK293,
Jurkat, K562 cancer cell lines and human topoisomerase I (hTop1) inhibitory activity in vitro were found for the
synthesized acids. A probable mechanism of topoisomerase I inhibition was hypothesized on the basis of in silico
studies resorting to docking.
