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

Vladimir A D'yakonov; Lilya U Dzhemileva; Regina A Tuktarova; Svetlana R Ishmukhametova; Milyausha M Yunusbaeva; Ilfir R Ramazanova; Usein M Dzhemilev

doi:10.2174/1871520616666161207154850

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

Anticancer Agents Med Chem. 2017;17(8):1126-1135. doi: 10.2174/1871520616666161207154850.

Authors

Vladimir A D'yakonov¹, Lilya U Dzhemileva², Regina A Tuktarova¹, Svetlana R Ishmukhametova¹, Milyausha M Yunusbaeva³, Ilfir R Ramazanova¹, Usein M Dzhemilev¹

Affiliations

¹ Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075, Ufa, Russian Federation.
² Department of Immunology and Human Reproductive Health, Bashkir State Medical University, 3 Lenin Street, 450003, Ufa, Russian Federation.
³ Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences 71 Prospect Oktyabrya, 450054, Ufa, Russian Federation.

PMID: 27928953
DOI: 10.2174/1871520616666161207154850

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.

Keywords: 1; 2-dienes; 5Z; 9Z-Dienoic acids; cancer cell lines; cross-cyclomagnesiation; docking; homogeneous catalysis; steroids; topoisomerase I inhibitors.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
DNA Topoisomerases, Type I / metabolism*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Fatty Acids, Unsaturated / chemistry
Fatty Acids, Unsaturated / pharmacology*
Humans
Molecular Docking Simulation
Molecular Structure
Steroids / chemistry
Steroids / pharmacology*
Structure-Activity Relationship
Topoisomerase I Inhibitors / chemical synthesis
Topoisomerase I Inhibitors / chemistry
Topoisomerase I Inhibitors / pharmacology*

Substances

Antineoplastic Agents
Fatty Acids, Unsaturated
Steroids
Topoisomerase I Inhibitors
DNA Topoisomerases, Type I