Synthesis and Carbonic Anhydrase I, II, IX, and XII Inhibition Studies with a Series of Cyclic Sulfonyl Guanidines.

Autor: Abdoli M; Institute of Chemistry and Chemical Technology, Faculty of Natural Sciences and Technology, Riga Technical University, P. Valdena iela 3, LV-1048, Riga, Latvia., Bonardi A; NEUROFARBA Department, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019, Florence, Italy., Supuran CT; NEUROFARBA Department, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019, Florence, Italy., Žalubovskis R; Institute of Chemistry and Chemical Technology, Faculty of Natural Sciences and Technology, Riga Technical University, P. Valdena iela 3, LV-1048, Riga, Latvia.; Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006, Riga, Latvia.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2024 Oct 01; Vol. 19 (19), pp. e202400197. Date of Electronic Publication: 2024 Aug 21.
DOI: 10.1002/cmdc.202400197
Abstrakt: A series of thirteen cyclic sulfonyl guanidines were prepared and evaluated against tumor-associated human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX and hCA XII, as well as against off-target cytosolic isoforms hCA I and hCA II. The compounds reported here were generally inactive against both off-target isoforms (K I >100 μM), while all of them moderately inhibited both target isoforms hCA IX and XII in the submicromolar to micromolar ranges in which K I values spanned from 0.57 to 8.4 μM against hCA IX and from 0.34 to 9.7 against hCA XII. Due to the notable selectivity of the title compounds toward isoforms hCA IX and XII, they can be considered as useful scaffolds for further chemical optimization to develop new highly selective antitumor agents.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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