Comparative in-vitro anti-inflammatory, anticholinesterase and antidiabetic evaluation: computational and kinetic assessment of succinimides cyano-acetate derivatives.

This research was planned to synthesize cyano-acetate derivatives of succinimide and evaluate its comparative biological efficacy as anti-inflammatory, anti-cholinesterase and anti-diabetic, which was further validated by molecular docking studies. The three cyano-acetate derivatives of succinimide including compound Methyl 2-cyano-2-(2,5-dioxopyrrolidin-3-yl)acetate, compound Methyl 2-cyano-2-(1-methyl-2,5-dioxopyrrolidin-3-yl)acetate and compound Methyl 2-cyano-2-(1-ethyl-2,5-dioxopyrrolidin-3-yl) acetate were synthesized. The mentioned compounds were checked for in vitro anti-inflammatory, anti-cholinesterase and anti-diabetic (α-amylase inhibition) activity. To validate the in vitro results, computational studies were carried out using molecular operating environment to analyse the BE, i.e. binding energies of all synthesized compounds against the respective enzymes. The Compounds exhibited anti-inflammatory via inhibiting COX-2 (IC value of 204.08, 68.60 and 50.93 µM, respectively), COX-1 (IC value of 287, 185, and 143 µM, respectively) and 5-LOX (IC value of 138, 50.76 and 20, 87 µM respectively) They exhibited choline-mimetic potential, such as compound inhibited AChE enzyme (IC value of 240, 174, and 134 µM, respectively) and BChE enzyme (IC value of 203, 134 and 97 µM, respectively). The Compounds exhibited anti-diabetic effect via inhibiting α-amylase enzyme (IC values of 250, 106 and 60 µM, respectively). Molecular docking studies revealed that the synthesized compounds have good binding affinity in the binding pockets of AChE, BChE, COX-2, 5-LOX and α-amylase enzyme and showed high binding energies. The synthesized succinimide derivatives, i.e. compound showed marked inhibitory activities against cyclooxygenase, lipoxygenase, α-amylase and cholinesterase enzymes. Among these three, compound and showed strong anti-inflammatory and anti-diabetic activity while they displayed moderate anti-cholinesterase activity supported by molecular docking results.Communicated by Ramaswamy H. Sarma.