Ferrocene Derivatives as Histone Deacetylase Inhibitors: Synthesis and Biological Evaluation

Ferrocene is an organometallic compound that has attracted considerable scientific interest due to its unique properties, including low toxicity, excellent stability in aqueous and aerobic media, and high lipophilicity, which enhances membrane permeability. The ferrocene moiety has been effectively...

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Main Authors: Rostislava Angelova, Georgi Stavrakov
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Organics
Subjects:
Online Access:https://www.mdpi.com/2673-401X/6/1/4
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author Rostislava Angelova
Georgi Stavrakov
author_facet Rostislava Angelova
Georgi Stavrakov
author_sort Rostislava Angelova
collection DOAJ
description Ferrocene is an organometallic compound that has attracted considerable scientific interest due to its unique properties, including low toxicity, excellent stability in aqueous and aerobic media, and high lipophilicity, which enhances membrane permeability. The ferrocene moiety has been effectively used as a bioisostere of phenyl rings and heteroaromatic groups in the structures of approved tyrosine kinase inhibitors and histone deacetylase inhibitors (HDACis). HDACis exert their cytotoxic effects by blocking cyclin/CDK complexes, causing cell cycle arrest, inducing apoptosis, inhibiting angiogenesis, and through non-histone-directed mechanisms. This mini-review summarizes the synthesis and biological evaluation of small libraries of compounds in which a ferrocenyl moiety is incorporated into the structure of suberoylanilide hydroxamic acid (SAHA) and a number of analogues. The influence of the organometallic function on the antiproliferative effect is investigated. Both docking analysis and in vitro studies confirm that the ferrocenyl-modified HDACis exhibit potent cytotoxicity and strong inhibitory activity against the various enzyme isoforms.
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spelling doaj-art-4e5844fdb7274812920ebef34481d0552025-08-20T03:43:40ZengMDPI AGOrganics2673-401X2025-01-0161410.3390/org6010004Ferrocene Derivatives as Histone Deacetylase Inhibitors: Synthesis and Biological EvaluationRostislava Angelova0Georgi Stavrakov1Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaFaculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaFerrocene is an organometallic compound that has attracted considerable scientific interest due to its unique properties, including low toxicity, excellent stability in aqueous and aerobic media, and high lipophilicity, which enhances membrane permeability. The ferrocene moiety has been effectively used as a bioisostere of phenyl rings and heteroaromatic groups in the structures of approved tyrosine kinase inhibitors and histone deacetylase inhibitors (HDACis). HDACis exert their cytotoxic effects by blocking cyclin/CDK complexes, causing cell cycle arrest, inducing apoptosis, inhibiting angiogenesis, and through non-histone-directed mechanisms. This mini-review summarizes the synthesis and biological evaluation of small libraries of compounds in which a ferrocenyl moiety is incorporated into the structure of suberoylanilide hydroxamic acid (SAHA) and a number of analogues. The influence of the organometallic function on the antiproliferative effect is investigated. Both docking analysis and in vitro studies confirm that the ferrocenyl-modified HDACis exhibit potent cytotoxicity and strong inhibitory activity against the various enzyme isoforms.https://www.mdpi.com/2673-401X/6/1/4ferroceneHDACSAHAbioorganometalliccancer
spellingShingle Rostislava Angelova
Georgi Stavrakov
Ferrocene Derivatives as Histone Deacetylase Inhibitors: Synthesis and Biological Evaluation
Organics
ferrocene
HDAC
SAHA
bioorganometallic
cancer
title Ferrocene Derivatives as Histone Deacetylase Inhibitors: Synthesis and Biological Evaluation
title_full Ferrocene Derivatives as Histone Deacetylase Inhibitors: Synthesis and Biological Evaluation
title_fullStr Ferrocene Derivatives as Histone Deacetylase Inhibitors: Synthesis and Biological Evaluation
title_full_unstemmed Ferrocene Derivatives as Histone Deacetylase Inhibitors: Synthesis and Biological Evaluation
title_short Ferrocene Derivatives as Histone Deacetylase Inhibitors: Synthesis and Biological Evaluation
title_sort ferrocene derivatives as histone deacetylase inhibitors synthesis and biological evaluation
topic ferrocene
HDAC
SAHA
bioorganometallic
cancer
url https://www.mdpi.com/2673-401X/6/1/4
work_keys_str_mv AT rostislavaangelova ferrocenederivativesashistonedeacetylaseinhibitorssynthesisandbiologicalevaluation
AT georgistavrakov ferrocenederivativesashistonedeacetylaseinhibitorssynthesisandbiologicalevaluation