Substituted benzene sulfonamides incorporating 1,3,5-triazinyl moieties potently inhibit human carbonic anhydrases II,IX and XII |
| |
Affiliation: | 1. Department of Pharmacy, “G. D''Annunzio” University of Chieti-Pescara, Chieti, Italy;2. Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy |
| |
Abstract: | A series of benzene sulfonamides incorporating 1,3,5-triazinyl moieties were synthesized using cyanuric chloride as starting material. Inhibition studies against human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II (cytosolic) and IX, XII (transmembrane, tumor-associated) isoforms were performed with the new compounds. hCA I was modestly inhibited (KIs in the range of 87 nM–4.35 μM), hCA II was moderately inhibited by most of the new compounds (KIs in the range of 12.5–130 nM), whereas the tumor associated isoforms were potently inhibited, with KIs in the range of 1.2–34.1 nM against hCA IX and of 2.1–33.9 against hCA XII, respectively. Docking studies of some of the new compounds showed an effective binding mode within the enzyme active site, as demonstrated earlier by X-ray crystallography for structurally-related sulfonamides incorporating 1,3,5-triazinyl functionalities. |
| |
Keywords: | Carbonic anhydrase 1,3,5-Triazine Benzene sulfonamides Isoform selectivity Enzyme inhibition Molecular docking |
本文献已被 ScienceDirect 等数据库收录! |
|