Transformations, NMR studies and biological testing of some 17β-isoxazolyl steroids and their heterocyclic ring cleavage derivatives

Alexander Baranovsky; Alesya Ladyko; Tatsiana Shkel; Sergey Sokolov; Natallia Strushkevich; Andrey Gilep

doi:10.1016/j.steroids.2020.108768

Transformations, NMR studies and biological testing of some 17β-isoxazolyl steroids and their heterocyclic ring cleavage derivatives

Steroids. 2021 Feb:166:108768. doi: 10.1016/j.steroids.2020.108768. Epub 2020 Nov 21.

Authors

Alexander Baranovsky¹, Alesya Ladyko², Tatsiana Shkel², Sergey Sokolov², Natallia Strushkevich³, Andrey Gilep²

Affiliations

¹ Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, Kuprevich Str. 5/2, 220143 Minsk, Belarus. Electronic address: baranovsky@iboch.by.
² Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, Kuprevich Str. 5/2, 220143 Minsk, Belarus.
³ Skolkovo Institute of Science and Technology, Bol'shoy Bul'var, 30, 143026 Moscow, Russia.

PMID: 33232722
DOI: 10.1016/j.steroids.2020.108768

Abstract

The synthesis and NMR structure analysis of a group of oxygenated steroids containing isoxazole, dihydrofuran, tetrahydrofuran rings or enamino carbonyl fragment in the side chain have been fulfilled. The prepared compounds were tested toward several enzymes (human cytochrome P450s CYP17, CYP19, CYP51 and CYP51 of pathogenic fungus Candida glabrata) as their potential inhibitors. A number steroids show a high level affinity (micro- and submicromole) for the enzyme-ligand complexes of the tested compounds with human CYP51, CYP19 and CYP51 of C. glabrata.

Keywords: Cytochrome P450; Dihydrofuran; Enamino ketone; Enzyme; Estradiol; Side chain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aromatase
Humans
Steroids
Sterol 14-Demethylase*

Substances

Steroids
Aromatase
CYP19A1 protein, human
Sterol 14-Demethylase