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Coumarin‐Thiourea Hybrids Show Potent Carbonic Anhydrase IX and XIII Inhibitory Action
Author(s) -
Thacker Pavitra S.,
Srikanth Danaboina,
Angeli Andrea,
Singh Priti,
Chinchilli Krishna Kartheek,
Arifuddin Mohammed,
Supuran Claudiu T.
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000915
Subject(s) - thiourea , coumarin , chemistry , carbonic anhydrase , gene isoform , cytosol , stereochemistry , enzyme , isozyme , biochemistry , organic chemistry , gene
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.