Crystal structure of 16-ferrocenylmethyl-3β-hydroxyestra-1,3,5(10)-trien-17-one: a potential chemotherapeutic drug

Abstract

A new ferrocene complex, 16-ferrocenylmethyl-3β-hy­droxy­estra-1,3,5(10)-trien-17-one, has been synthesized and structurally characterized by single-crystal X-ray diffraction techniques. The ferrocenylmethyl group is positioned at the β face of the estrone moiety; as a result, a new stereogenic center is formed leading to an R stereochemical configuration. No head-to-tail hydrogen bonding is observed in the crystal packing, as is the case in estrone and other derivatives.

Synthesis and structural studies of 16‐ferrocenemethyl‐estra‐1,3,5(10)‐triene‐3,17β‐diol and its interaction with human serum albumin by fluorescence spectroscopy and in silico docking approaches

“…The solid‐state crystal structure of the ferrocene conjugate I , 16‐ferrocenemethyl‐3β‐hydroxy‐estra‐1,3,5(10)‐triene‐17‐one, was previously presented by our group . Such a structure confirms the selective reduction of the carbon–carbon double bond (C 16 = C 19 ) using only one stereogenic center at position 16 (R–C 16 ) of the estrone, thus, positioning the ferrocenemethyl group at the beta face of the steroid.…”

“…As a new approach to rationalize the metal‐based drug design, ferrocene has been incorporated into the principal structural component of natural and synthetic compounds with biological activity to develop more selective and effective metal‐based drugs . This approach has been applied in hormone‐dependent breast cancer, in which ferrocene has been vectorized with estrogen hormones in order to effectively deliver its moiety to cancer tissues . In this work, we aimed to explore position 16 of the estrogen hormone as part of the efforts to synthetize, characterize, and apply ferrocene–hormone conjugates in hormone‐dependent breast cancer.…”

“…The aim of this study was to determine the thermodynamic parameters involved in the molecular recognition as well as to generate detailed information on the strength of individual bonding interactions and their contribution to the overall free energy of complexation. The synthesis and X‐ray crystal structure of its precursor, 16‐ferrocenylmethyl‐3‐hydroxy‐estra‐1,3,5(10)‐triene‐17‐one ( I ), was previously presented as a probe of unequivocal fixed stereochemistry configuration at C 16 of the estrone moiety. The crystallographic data of II confirm the diastereoselective reduction of the carbonyl group (C 17 –O 2 ) of I .…”

3-Ferrocenyl-estra-1,3,5 (10)-triene-17-one: Synthesis, Crystal Structure, Hirshfeld Surface Analysis, DFT Studies, and Its Binding to Human Serum Albumin Studied through Fluorescence Quenching and In Silico Docking Studies

“…This organometallic compound forms radical oxygen species (ROS) that cause oxidative damage to DNA, inducing cell apoptosis [ 5 ]. Our research group has successfully incorporated ferrocene at estrogen’s rings A and D, showing antiproliferative effects in vitro on hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell lines [ 6 , 7 , 8 , 9 , 10 , 11 ].…”

Screening of ferrocenyl–phosphines identifies a gold-coordinated derivative as a novel anticancer agent for hematological malignancies

“…6 While these molecules exhibited signicant but low antitumor efficacy in mice, results suggested that the incorporation of the ferrocenyl group into an appropriate carrier could provide an organometallic compound with enhanced antitumor activity. [6][7][8] Noteworthy from this perception, a novel molecule "ferrocifen" was developed by integrating ferrocene into the tamoxifen scaffold that exhibited signicant cytotoxicity in ER+ MCF-7, a breast cancer cell line resistant to common anti-estrogenic drugs. [9][10][11] Furthermore, phosphines coordinated to transition metal salts have received extensive interest in anticancer studies following the tremendous success of the blockbuster drug "cisplatin".…”