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A Multitargeted Approach: Organorhodium Anticancer Agent Based on Vorinostat as a Potent Histone Deacetylase Inhibitor.

Authors :
Hanif, Muhammad
Arshad, Jahanzaib
Astin, Jonathan W.
Rana, Zohaib
Zafar, Ayesha
Movassaghi, Sanam
Leung, Euphemia
Patel, Kamal
Söhnel, Tilo
Reynisson, Jóhannes
Sarojini, Vijayalekshmi
Rosengren, Rhonda J.
Jamieson, Stephen M. F.
Hartinger, Christian G.
Source :
Angewandte Chemie International Edition. 8/17/2020, Vol. 59 Issue 34, p14609-14614. 6p.
Publication Year :
2020

Abstract

The combination of more than one bioactive moiety in a multitargeted anticancer agent may result in synergistic activity of its components. Using this concept, bioorganometallic compounds were designed to feature a metal center, a 2‐pyridinecarbothioamide (PCA), and a hydroxamic acid, which is found in the anticancer drug vorinostat (SAHA). The organometallics showed inhibitory activity in the nanomolar range against histone deacetylases (HDACs) as the key target for SAHA. In particular, the Rh complex was a potent inhibitor of HDAC6 over HDAC1 and HDAC8. Whereas this complex was highly cytotoxic in human cancer cells, it showed low toxicity in hemolysis studies and zebrafish, demonstrating the role of the metal center. For this complex a slightly reduced expression of vascular endothelial growth factor receptor 2 (VEGFR2) was established, which was upregulated by SAHA. This finding indicates that the new organometallics display different modes of action than their bioactive components. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14337851
Volume :
59
Issue :
34
Database :
Academic Search Index
Journal :
Angewandte Chemie International Edition
Publication Type :
Academic Journal
Accession number :
145051763
Full Text :
https://doi.org/10.1002/anie.202005758