Discovery of First-in-Class Carbonic Anhydrase/Histone Deacetylase Dual Inhibitors with Antiproliferative Activity in Cancer Cells
This study reports <i>in vitro</i> 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.
Authors
- Rino Ragno (ORCID: https://orcid.org/0000-0001-5399-975X)
- Daniela Trisciuoglio (ORCID: https://orcid.org/0000-0002-7007-7914)
- Antonello Mai (ORCID: https://orcid.org/0000-0001-9176-2382)
- Silvia Peppicelli (ORCID: https://orcid.org/0000-0001-6459-0458)
- Lido Calorini (ORCID: https://orcid.org/0000-0002-5508-4200)
- Clemens Zwergel (ORCID: https://orcid.org/0000-0002-3097-0003)
- Murat Bozdağ (ORCID: https://orcid.org/0000-0002-5010-0355)
- Elena Andreucci (ORCID: https://orcid.org/0000-0003-3980-3073)
- Alessio Biagioni (ORCID: https://orcid.org/0000-0002-6193-7417)
- Fabrizio Carta (ORCID: https://orcid.org/0000-0002-1141-6146)
- Sérgio Valente (ORCID: https://orcid.org/0000-0002-2241-607X)
- Andrea Angeli (ORCID: https://orcid.org/0000-0002-1470-7192)
- Roberta Astolfi (ORCID: https://orcid.org/0009-0002-0199-7730)
- Alessia Raucci (ORCID: https://orcid.org/0000-0003-4182-4420)
- Lidia Giuliani
- Nabil Mroweh
Institutions
- Institute of Molecular Biology and Pathology (IT)
- Istituto Nazionale di Fisica Nucleare, Sezione di Firenze (IT)
- Istituto Pasteur (IT)
- National Research Council (IT)
- University of Florence (IT)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2025-10-28
- DOI
- https://doi.org/10.1021/acs.jmedchem.5c01788
- Citations
- 2
- Primary Topic
- Enzyme function and inhibition
- Type
- article
- Field-Weighted Citation Impact
- 1.61