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

ChemMedChem 2024
Morteza Abdoli, Alessandro Bonardi, Claudiu T. Supuran, Raivis Žalubovskis

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 (KI>100 μM), while all of them moderately inhibited both target isoforms hCA IX and XII in the submicromolar to micromolar ranges in which KI 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.

Atslēgas vārdi
Antitumor agents | Cancer-related isoforms | Carbonic anhydrase inhibitors | Sulfaguanidines | Sulfonamides
DOI
10.1002/cmdc.202400197
Hipersaite
https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202400197

Abdoli, M., Bonardi, A., Supuran, C., Žalubovskis, R. Synthesis and Carbonic Anhydrase I, II, IX, and XII Inhibition Studies with a Series of Cyclic Sulfonyl Guanidines. ChemMedChem, 2024, Vol. 19, No. 19, Article number e202400197. ISSN 1860-7179. e-ISSN 1860-7187. Pieejams: doi:10.1002/cmdc.202400197

Publikācijas valoda
English (en)