Synthesis and Enzyme Inhibitory Activity of Novel Pyridine-2,6-dicarboxamides Bearing Primary Sulfonamide Groups

Abstract

New pyridine-2,6-dicarboxamide derivatives containing sulfonamide groups were synthesized by the coupling of pyridine-2,6-dicarbonyl dichloride and various aminobenzenesulfonamides in a mixture of dichloromethane and acetone. The pyridinedicarboxamide-based sulfonamides were evaluated as carbonic anhydrase (CA) and cholinesterase (ChE) inhibitors, and they showed IC₅₀ values in the ranges 12.8–37.6 nM against human carbonic anhydrase I (hCA I), 17.8–46.7 nM against human carbonic anhydrase II (hCA II), 98.4–197.5 nM against acetylcholinesterase (AChE), and 82.2–172.7 nM against butyrylcholinesterase (BuChE). These results are comparable with those for known inhibitors such as acetazolamide (IC₅₀ = 32.1 nM for hCA I and IC₅₀ = 51.0 nM for hCA II) and rivastigmine (IC₅₀ = 60.2 nM for AChE and IC₅₀ = 14.0 nM for BuChE), which qualifies the synthesized compounds as candidates for a more in-depth study.