Facile synthesis of two azete-steroid derivatives and theoretical evaluation of its interaction with the aromatase enzyme

Year 2019, , 415 - 428, 01.12.2019

Figueroa Lauro Diaz Francisco Rosas Nexticapa Garcimarrero Alejandra Mateu Virginia Hernandez Patricia Pool Eduardo Lopez Ramos Hau Lenin Borges Yaritza

https://doi.org/10.15671/hjbc.602183

Abstract

Several aromatase inhibitors
have used for the treatment of breast cancer; however, some of these drugs may
produce some side effects such as endometrial cancer and bone loss. The aim of
this study was to synthesize two new azete-steroid derivatives (compounds 9
or 10) to evaluate its theoretical interaction with an aromatase enzyme
(2wd3) using anastrozole and exemestane as controls in a docking model. The
preparation of 9 and 10 was carried out using a series of
reactions which involves amination, etherification, nitration, and addition.
Chemical structure of the compounds was confirmed using elemental analysis and
NMR spectrum. The results showed that compounds 9 or 10 could
bind to a different type of aminoacid residues involved in of 2wd3 protein
surface compared anastrozole and exemestane; this phenomenon may exert changes
in the biological activity of aromatase enzyme. All data suggest that compounds
9 or 10 could be an alternative for the treatment of breast
cancer.

Keywords

Azete, steroid, derivative

Supporting Institution

University Autonomous of Campeche

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