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.
Discovery of first-in-class carbonic anhydrase/histone deacetylase dual inhibitors with antiproliferative activity in cancer cells / Bozdag, M., Mroweh, N., Raucci, A., Angeli, A., Peppicelli, S., Biagioni, A., Calorini, L., Trisciuoglio, D., Ragno, R., Astolfi, R., Giuliani, L., Zwergel, C., Valente, S., Andreucci, E., Carta, F., Mai, A., Supuran, C.T.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 68:21(2025), pp. 22874-22895. [10.1021/acs.jmedchem.5c01788]
Discovery of first-in-class carbonic anhydrase/histone deacetylase dual inhibitors with antiproliferative activity in cancer cells
Raucci, Alessia;Ragno, Rino;Astolfi, Roberta;Giuliani, Lidia;Zwergel, Clemens;Valente, Sergio
;Mai, Antonello;
2025
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.| File | Dimensione | Formato | |
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Bozdag_Discovery_2025.pdf
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