A Journey Around Boronic Acids: Sulfonyl Hydrazone‐Containing Derivatives as Carbonic Anhydrase Inhibitors DOI

Deniz Akin Anakok,

Andrea Angeli, Ilaria D’Agostino

et al.

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(4)

Published: April 1, 2025

ABSTRACT Recently, a rising interest in boronic acids and their derivatives was recorded the Medicinal Chemistry field due to high versatility broad applicability as bioactive compounds several diseases, including cancer microbial infections. The ability of acid moieties bind zinc ions first hypothesized by inhibitory activity bortezomib, boron‐containing protease inhibitor, on different isoforms Carbonic Anhydrase (CA, EC: 4.2.1.1) enzyme family then assessed through X‐ray crystallographic studies benzoxaboroles complex with hCA II. These findings, along overexpression IX XII hypoxic and, particular, breast cancer, drove us explore chemical space around phenylboronic generating focused library 16 (1–4a–d) decorated alkyl sulfonyl hydrazones. were subjected stopped flow‐based inhibition assays panel hCAs, tumor‐associated isoforms, revealing low micromolar constants ( K I s) some cases. However, antiproliferative conducted human triple‐negative cell line showed lack at tested concentrations.

Language: Английский

Polypharmacology of carbonic anhydrase inhibitors and activators DOI
Alessandro Bonardi, Claudiu T. Supuran

Expert Opinion on Pharmacotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 14

Published: March 1, 2025

Introduction Carbonic anhydrases (CAs) are enzymes involved in many physiologic and pathological processes connected with a diversity of conditions. Many their inhibitors used clinically for the management glaucoma, epilepsy, obesity, cancer. Some these compounds also show significant polypharmacological effects. CA activators (CAAs) not clinical use.

Language: Английский

Citations

0
-Derivatization of Natural Tropolone and β-Thujaplicin Leading to effective Inhibitors of Human Carbonic Anhydrases IX and XII DOI Creative Commons
Francesco Melfi, Ilaria D’Agostino, Simone Carradori

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117552 - 117552

Published: March 1, 2025

Language: Английский

Citations

0
A Journey Around Boronic Acids: Sulfonyl Hydrazone‐Containing Derivatives as Carbonic Anhydrase Inhibitors DOI

Deniz Akin Anakok,

Andrea Angeli, Ilaria D’Agostino

et al.

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(4)

Published: April 1, 2025

ABSTRACT Recently, a rising interest in boronic acids and their derivatives was recorded the Medicinal Chemistry field due to high versatility broad applicability as bioactive compounds several diseases, including cancer microbial infections. The ability of acid moieties bind zinc ions first hypothesized by inhibitory activity bortezomib, boron‐containing protease inhibitor, on different isoforms Carbonic Anhydrase (CA, EC: 4.2.1.1) enzyme family then assessed through X‐ray crystallographic studies benzoxaboroles complex with hCA II. These findings, along overexpression IX XII hypoxic and, particular, breast cancer, drove us explore chemical space around phenylboronic generating focused library 16 (1–4a–d) decorated alkyl sulfonyl hydrazones. were subjected stopped flow‐based inhibition assays panel hCAs, tumor‐associated isoforms, revealing low micromolar constants ( K I s) some cases. However, antiproliferative conducted human triple‐negative cell line showed lack at tested concentrations.

Language: Английский

Citations

0