Coumarin‐Thiourea Hybrids Show Potent Carbonic Anhydrase IX and XIII Inhibitory Action

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.

Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies

“…These include sulfonamido carboranes 134 , 135 , benzenesulfonamides incorporating 1,3,4-oxadiazole hybrids 136 , benzimidazole derivatives 137 , 7-Acylamino-3H-1,2-benzoxathiepine 2,2-dioxides 138 , aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide 139 , S-substituted 2-mercaptoquinazolin-4(3H)-ones and 4-ethylbenzensulfonamides 140 , aryl selenols 141 , sulfocoumarins and coumarin derivatives 142–145 , coumarin-thiourea hybrids 146 , phenols, polyamines, carboxylates 147 , epacadostat 148 , pyridinium derivatives of 3-aminobenzenesulfonamide and sulfonamides containing various nitrogenous bases 11 , 149 , 150 and short peptide-constructed nanofibers 151 .…”

Design and development of novel series of indole‐3‐sulfonamide ureido derivatives as selective carbonic anhydrase II inhibitors

“…[18] After that, the nitro group at position-5 of N-alkylated indole-3-sulfonamide was reduced in the presence of iron powder and acetic acid to obtain N-alkylated 5-aminoindole-3sulfonamide 5. [19] Finally, the target compounds 6a-ag were obtained in good quantity by reacting 5 with different isocyanates. [20] In this study, 33 compounds were synthesized, and their structures were confirmed by 1 H NMR (nuclear magnetic resonance), 13 C NMR, and high-resolution mass spectrometry (HRMS).…”

Ureidosulfocoumarin Derivatives As Selective and Potent Carbonic Anhydrase IX and XII Inhibitors

“…The α‐CAs are found in vertebrates, protozoa, algae, and cytoplasm of green plants and in many Gram negative bacteria; the β‐CAs predominantly present in both Gram negative and positive bacteria algae and chloroplasts of mono‐ as well as di‐cotyledons, and also in many fungi and Archaea . The γ‐CAs are mainly seen in archaea, cyanobacteria and most types of bacteria; whereas the δ‐, ζ ‐ and θ‐CAs seem to be present only in marine diatoms, whereas the η ‐CAs in protozoa and the ι‐CAs are found in marine diatoms and bacteria [2–5] . Among all families only the α‐CAs class which is present in human and a total of 16 isozymes have been determined as members of the α‐CA family in mammals represented by human carbonic anhydrase (hCA) varies from hCA I to hCA XV.…”