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.
Coumarin-Thiourea Hybrids Show Potent Carbonic Anhydrase IX and XIII Inhibitory Action / Thacker P.S.; Srikanth D.; Angeli A.; Singh P.; Chinchilli K.K.; Arifuddin M.; Supuran C.T.. - In: CHEMMEDCHEM. - ISSN 1860-7179. - ELETTRONICO. - 16:(2021), pp. 1252-1256. [10.1002/cmdc.202000915]
Coumarin-Thiourea Hybrids Show Potent Carbonic Anhydrase IX and XIII Inhibitory Action
Angeli A.;Supuran C. T.
2021
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.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.