2H-chromene and 7H-furo-chromene Derivatives Selectively Inhibit Tumour Associated Human Carbonic Anhydrase IX and XII Isoforms

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2023 Oct 23

PMID 37870190

Authors

Lisa Sequeira

Simona Distinto

Rita Meleddu

Marco Gaspari

Andrea Angeli

Filippo Cottiglia

Daniela Secci

Alessia Onali

Erica Sanna

Fernanda Borges

Eugenio Uriarte

Stefano Alcaro

Claudiu T Supuran

Elias Maccioni

Affiliations

Soon will be listed here.

Abstract

Tumour associated carbonic anhydrases (CAs) IX and XII have been recognised as potential targets for the treatment of hypoxic tumours. Therefore, considering the high pharmacological potential of the chromene scaffold as selective ligand of the IX and XII isoforms, two libraries of compounds, namely 2H-chromene and 7H-furo-chromene derivatives, with diverse substitution patterns were designed and synthesised. The structure of the newly synthesised compounds was characterised and their inhibitory potency and selectivity towards human CA off target isoforms I, II and cancer-associated CA isoforms IX and XII were evaluated. Most of the compounds inhibit CA isoforms IX and XII with no activity against the I and II isozymes. Thus, while the potency was influenced by the substitution pattern along the chromene scaffold, the selectivity was conserved along the series, confirming the high potential of both 2H-chromene and 7H-furo-chromene scaffolds for the design of isozyme selective inhibitors.

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