Coumarin‐Thiourea Hybrids Show Potent Carbonic Anhydrase IX and XIII Inhibitory Action. (9th February 2021)

• Record Type: Journal Article
• Authors: Thacker, Pavitra S.; Srikanth, Danaboina; Angeli, Andrea; Singh, Priti; Chinchilli, Krishna Kartheek; Arifuddin, Mohammed; Supuran, Claudiu T.
• Is Part Of: ChemMedChem. Volume 16:Number 8(2021)
• Page Start: 1252
• Page End: 1256
• Publication Date: 2021-02-09
• Subjects: carbonic anhydrases -- coumarin -- hCA -- thiourea; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202000915
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: A series of coumarin‐thiourea hybrids (4 a –o ) has been synthesized, and the compounds have been evaluated against the tumour associated transmembrane isoform, human (h) carbonic anhydrase (CA) hCA IX and the less‐explored cytosolic isoform, hCA XIII. All compounds exhibited potent inhibition of both isoforms, with K I values of <100 nM against hCA IX. Compound 4 b was the best inhibitor ( K I =78.5 nM). All the compounds inhibited hCA XIII in the low‐nanomolar to sub‐micromolar range, with compound 4 b again showing the best inhibition ( K I =76.3 nM). With compound 4 b as a lead, more‐selective inhibitors of hCA IX and hCA XIII or dual hCA IX/XIII inhibitors might be developed. Abstract : Two for the price of one : A series of coumarin‐thiourea hybrids (4 a –o ) has been synthesized and evaluated for their inhibitory potencies against two carbonic anhydrases: the transmembrane tumor‐associated isoform, hCA IX and the cytosolic isoform, XIII. The compounds inhibited both isoforms in the low‐to‐high nanomolar range.