A novel series of imidazothiadiazole-linked benzenesulfonamide derivatives (5a–t) was synthesized and subjected for screening against the four physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms: hCA I, II, VA, and IX. The compounds selectively inhibited hCA I and II over hCA VA and IX. Furthermore, among the two cytosolic isoforms, hCA II was more effectively inhibited as compared with hCA I. The most active compounds were 5o with Ki = 0.246 µM and 5p with Ki = 0.376 µM against hCA II, whereas compound 5f showed good inhibition against both hCA I and II with Ki = 0.493 and 0.4 µM, respectively. This class of underexplored sulfonamides may be used to design isoform-selective CA inhibitors targeting enzymes of medicinal chemistry interest.

Design and synthesis of benzenesulfonamide-linked imidazo[2,1-b][1,3,4]thiadiazole derivatives as carbonic anhydrase I and II inhibitors / Swain B.; Aashritha K.; Singh P.; Angeli A.; Kothari A.; Sigalapalli D.K.; Yaddanapudi V.M.; Supuran C.T.; Arifuddin M.. - In: ARCHIV DER PHARMAZIE. - ISSN 0365-6233. - ELETTRONICO. - 354:(2021), pp. 2100028.2100028-2100028.2100028. [10.1002/ardp.202100028]

Design and synthesis of benzenesulfonamide-linked imidazo[2,1-b][1,3,4]thiadiazole derivatives as carbonic anhydrase I and II inhibitors

Singh P.;Angeli A.;Supuran C. T.;
2021

Abstract

A novel series of imidazothiadiazole-linked benzenesulfonamide derivatives (5a–t) was synthesized and subjected for screening against the four physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms: hCA I, II, VA, and IX. The compounds selectively inhibited hCA I and II over hCA VA and IX. Furthermore, among the two cytosolic isoforms, hCA II was more effectively inhibited as compared with hCA I. The most active compounds were 5o with Ki = 0.246 µM and 5p with Ki = 0.376 µM against hCA II, whereas compound 5f showed good inhibition against both hCA I and II with Ki = 0.493 and 0.4 µM, respectively. This class of underexplored sulfonamides may be used to design isoform-selective CA inhibitors targeting enzymes of medicinal chemistry interest.
2021
354
2100028
2100028
Swain B.; Aashritha K.; Singh P.; Angeli A.; Kothari A.; Sigalapalli D.K.; Yaddanapudi V.M.; Supuran C.T.; Arifuddin M.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1305607
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