Examination of the effects of five-membered heterocyclic active methylene compounds on metabolic enzymes

The inhibitory effects of thiazolidin-2,4-dione, rhodanine, hydantoin, 2-thiohydantoin, 3-aminorhodanine, and creatinine derivatives on various enzymes were evaluated using experimental and computational approaches. The activities of these compounds against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase, carbonic anhydrase isoenzymes (hCA I and hCA II), collagenase, and elastase were determined, together with their metal chelating capacities. In AChE inhibition studies, hydantoin was identified as the most potent inhibitor with an IC₅₀ value of 352.1 nM, while creatinine (830.3 nM) and hydantoin (846.1 nM) exhibited inhibitory effects comparable to the reference inhibitor tacrine against BChE. For α-glucosidase, thiazolidin-2,4-dione showed the closest activity to acarbose with an IC₅₀ value of 0.53 µM. Regarding carbonic anhydrase hCA II, creatinine (144.9 nM) and thiazolidin-2,4-dione (277.1 nM) emerged as more potent inhibitors than the reference compound acetazolamide. In elastase inhibition assays, thiazolidin-2,4-dione demonstrated the closest activity to the standard inhibitor EGCG with an IC₅₀ value of 5.38 µM. Molecular docking results revealed that compounds bearing hydantoin and thiazolidin-2,4-dione scaffolds bind more stably to the active sites of the target proteins. Overall, these findings indicate that the investigated structures hold promise for drug development application.