2. Academic Validation
  3. Discovery of First-in-Class Carbonic Anhydrase/Histone Deacetylase Dual Inhibitors with Antiproliferative Activity in Cancer Cells

Discovery of First-in-Class Carbonic Anhydrase/Histone Deacetylase Dual Inhibitors with Antiproliferative Activity in Cancer Cells

  • J Med Chem. 2025 Nov 13;68(21):22874-22895. doi: 10.1021/acs.jmedchem.5c01788.
Murat Bozdag 1,  Nabil Mroweh 1,  Alessia Raucci 2,  Andrea Angeli 1,  Silvia Peppicelli 3,  Alessio Biagioni 3,  Lido Calorini 3,  Daniela Trisciuoglio 4,  Rino Ragno 2,  Roberta Astolfi 2,  Lidia Giuliani 2,  Clemens Zwergel 2,  Sergio Valente 2,  Elena Andreucci 3,  Fabrizio Carta 1,  Antonello Mai 2 5,  Claudiu T Supuran 1
Affiliations

Affiliations

  • 1 Università Degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche E Nutraceutiche, Via Ugo Schiff 6, Sesto Fiorentino, Florence I-50019, Italy.
  • 2 Department of Drug Chemistry & Technologies, Sapienza University of Rome, P. le a Moro 5, Rome 00185, Italy.
  • 3 Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence 50134, Italy.
  • 4 Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR), Rome 00185, Italy.
  • 5 Pasteur Institute, Cenci-Bolognetti Foundation, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome 00185 Italy.
PMID: 41150938 DOI: 10.1021/acs.jmedchem.5c01788
Abstract

This study reports in vitro evidence supporting a new class of compounds capable of independently targeting the tumor-associated human (h) Carbonic Anhydrase (CA; EC 4.2.1.1) and histone deacetylase (HDAC; EC 3.5.1.98) isoforms as first-in-class agents endowed with enhanced antiproliferative effects and safety profiles when compared to their constitutive counterparts as well as to clinically used drugs. The binding modes of both the CA- and HDAC-directed moieties were investigated through X-ray and molecular modeling experiments, respectively, thus delivering detailed Structure-Activity Relationship (SAR) knowledge.

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