Issue 18, 2019

Synthesis, structure, docking and cytotoxic studies of ferrocene–hormone conjugates for hormone-dependent breast cancer application

Abstract

Previously, ferrocene incorporation into the principal structural component of biologically active molecules resulted in enhanced cytotoxic activity against hormone-dependent MCF-7 and T-47D and hormone-independent MDA-MB-231 breast-cancer cell lines. Here we explore 4 new ferrocene estrogen conjugates at position 16 of the estrogen hormone and compared them to the previously reported ferrocene estrogen conjugate 3-ferrocenyl-estra-1,3,5(10)-triene-17β-ol. The ferrocene conjugate 16-ferrocenylidene-3-hydroxyestra-1,3,5(10)-trien-17-one was synthesized using estrone and ferrocene carboxaldehyde as starting materials in 86% yield. This ferrocene complex was used as the starting material for the synthesis of new ferrocene estrogen conjugates by a short linker group at position 16 of the estrogen hormone. The position and stereochemistry of the linker was verified by its crystal structure. The ferrocene redox behavior, in vitro studies on breast-cancer cell lines and docking studies on ERα are presented. The data suggest that the ferrocene conjugates presented, either at position 3 or 16 of the estrogen, could serve as vectors and can be recognized by ERα as a delivery mechanism into the cell. These new ferrocene hormone conjugates showed cytotoxic activity comparable to that of conventional therapeutic drugs such as tamoxifen and cisplatin.

Graphical abstract: Synthesis, structure, docking and cytotoxic studies of ferrocene–hormone conjugates for hormone-dependent breast cancer application

Supplementary files

Article information

Article type
Paper
Submitted
08 май 2018
Accepted
21 ное 2018
First published
22 ное 2018

Dalton Trans., 2019,48, 5952-5964

Author version available

Synthesis, structure, docking and cytotoxic studies of ferrocene–hormone conjugates for hormone-dependent breast cancer application

J. A. Carmona-Negrón, A. Santana, A. L. Rheingold and E. Meléndez, Dalton Trans., 2019, 48, 5952 DOI: 10.1039/C8DT01856A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements