Inhibition Profiles of Some Novel Sulfonamide-Incorporated α-Aminophosphonates on Human Carbonic Anhydrases

ACS Medicinal Chemistry Letters 2023
Marjan Sobati, Morteza Abdoli, Alessandro Bonardi, Paola Gratteri, Claudiu T. Supuran, Raivis Žalubovskis

A series of hitherto unknown sulfonamide-incorporated α-aminophosphonate derivatives were synthesized through the one-pot, two-step FeCl3-catalyzed coupling of 4-aminobenzenesulfonamide with the appropriate benzaldehydes and diethyl phosphite. The new sulfonamides inhibition studies were performed on four carbonic anhydrase isoforms, i.e., the cytosolic human (h) hCA I and II (off-targets) as well as transmembrane cancer-related hCA IX and XII (targets). Among the synthesized compounds, derivative 23 resulted in the most selective compound against both cancer-associated isoforms over the off-target hCA I (hCA I/IX = 78; hCA I/XII = 458) and hCA II (hCA II/IX = 10; hCA II/XII = 56) and the binding mode of both enantiomers R and S was investigated in silico.

Keywords
Carbonic anhydrases | Docking | In silico | Sulfonamides | Tail approach | Tumor-related isoforms | α-Aminophosphonates
DOI
10.1021/acsmedchemlett.3c00200
Hyperlink
https://pubs.acs.org/doi/10.1021/acsmedchemlett.3c00200

Sobati, M., Abdoli, M., Bonardi, A., Gratteri, P., Supuran, C., Žalubovskis, R. Inhibition Profiles of Some Novel Sulfonamide-Incorporated α-Aminophosphonates on Human Carbonic Anhydrases. ACS Medicinal Chemistry Letters, 2023, Vol. 14, No. 8, pp.1067-1072. ISSN 1948-5875. Available from: doi:10.1021/acsmedchemlett.3c00200

Publication language
English (en)