Coumarin-Thiourea Hybrids Show Potent Carbonic Anhydrase IX and XIII Inhibitory Action |
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| Authors: | Pavitra S Thacker Danaboina Srikanth Dr Andrea Angeli Priti Singh Krishna Kartheek Chinchilli Dr Mohammed Arifuddin Prof Claudiu T Supuran |
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| Affiliation: | 1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana State, India;2. Università degli Studi di Firenze, Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy |
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| 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 KI values of <100 nM against hCA IX. Compound 4 b was the best inhibitor (KI=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 (KI=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. |
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| Keywords: | carbonic anhydrases coumarin hCA thiourea |
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