2 H ‐Indazolo [2,1‐ b ]phthalazine‐trione derivatives: Inhibition on some metabolic enzymes and molecular docking studies

In this study, substituted 2H‐indazolo[2,1‐ b ]phthalazine‐1,6,11‐trione compounds ( 4a–d ) obtained via one‐pot three‐component condensation reaction of aromatic aldehydes, cyclic 1,3‐dione, and phthalhydrazide in ethanol catalyzed by Y(OTf) 3 showed satisfactory inhibitory effects against some important enzymes. Also, these molecules had K i values in the row of 185.92 ± 36.03‐294.82 ± 50.76 nM vs carbonic anhydrase I (CA I), 204.93 ± 46.90‐374.10 ± 83.63 nM against human CA II, 937.16 ± 205.82‐1021.83 ± 193.66 nM against α‐glycosidase (α‐Gly), respectively. For cholinesterase enzymes, the K i values were found in the range of 47.26 ± 9.62‐72.05 ± 19.47 nM against acetylcholinesterase (AChE) and 65.03 ± 9.88‐102.83 ± 25.04 nM against butyrylcholinesterase (BChE), respectively. The inhibition effects of these compounds against enzymes whose name are AChE, BChE, α‐Gly, hCA I, and hCA II, were compared with control molecules like tacrine, acarbose, and acetazolamide.