Design, synthesis, SAR, and biological evaluation of saccharin-based hybrids as carbonic anhydrase inhibitors.

Autor: Chinchilli KK; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India., Royyala VN; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India., Thacker PS; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India., Angeli A; Neurofarba Department, Sezione di Scienze, Farmaceutiche e Nutraceutiche, Università Degli Studi di Firenze, Florence, Italy., Danaboina S; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India., Singh P; Process Chemistry Process Technology, Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India., Nanduri S; Process Chemistry Process Technology, Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India., Supuran CT; Neurofarba Department, Sezione di Scienze, Farmaceutiche e Nutraceutiche, Università Degli Studi di Firenze, Florence, Italy., Arifuddin M; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.; Department of Chemistry, Directorate of Distance Education, Maulana Azad National Urdu University, Hyderabad, India.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2022 Aug; Vol. 355 (8), pp. e2200019. Date of Electronic Publication: 2022 Apr 28.
DOI: 10.1002/ardp.202200019
Abstrakt: 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.
(© 2022 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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