Design, synthesis, SAR, and biological evaluation of saccharin‐based hybrids as carbonic anhydrase inhibitors. Issue 8 (28th April 2022)

• Record Type: Journal Article
• Authors: Chinchilli, Krishna K.; Royyala, Venkata N.; Thacker, Pavitra S.; Angeli, Andrea; Danaboina, Srikanth; Singh, Priti; Nanduri, Srinivas; Supuran, Claudiu T.; Arifuddin, Mohammed
• Is Part Of: Archiv der Pharmazie. Volume 355:Issue 8(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-04-28
• Subjects: 1, 2, 3‐triazole -- 1, 2, 4‐oxadiazole -- acetazolamide -- carbonic anhydrase -- saccharin; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202200019
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: Saccharin is a cyclic secondary sulfonamide, which is a selective inhibitor of the tumor‐associated carbonic anhydrase (CA; EC 4.2.1.1) enzymes CA IX and CA XII compared to many primary sulfonamides. In this study, new saccharin‐1, 2, 3‐triazole and saccharin‐1, 2, 4‐oxadiazole hybrids were synthesized. All the newly synthesized molecules were screened for their CA‐inhibitory activity against four important human CA (hCA) isoforms: hCA I, hCA II, hCA IX, and hCA XII. Compounds 8a and 8f emerged as potent hCA II inhibitors ( K i = 3 µM). Compounds 6d, 6e and 7a, 7b were highly selective against hCA IX (6d, 6e ) and hCA II (7a, 7b ), with moderate inhibitory activity. The activity of these compounds was further confirmed by performing in silico docking studies against hCA II and hCA IX. Abstract : New saccharin‐1, 2, 3‐triazole and saccharin‐1, 2, 4‐oxadiazole hybrids were synthesized and screened for their inhibitory activity against four important isoforms of human carbonic anhydrase (hCA): hCA I, hCA II, hCA IX, and hCA XII. Compounds 8a and 8f emerged as potent hCAII inhibitors, whereas compounds 6d, 6e and 7a, 7b were highly selective against hCAIX and hCAII, respectively, with moderate inhibitory activity.