Molecular Docking and Synthesis of 1, 2, 4 - Triazin Analogue of Diclofenac as Potential Ligand for Chlorpromazine Induced Parkinson’s in Rat Model

Aim: Parkinson’s disease (PD) is a common neurodegenerative disorder, which is characterized by slowly progressive loss of dopaminergic neurons associated with substantial. The present study was aimed for molecular docking and synthesis of 1, 2, 4–Triazin analogue of diclofenac as potential ligand for chlorpromazine induced Parkinson’s in rat model. Materials and methods: Twenty four Albino Wistar male Rats weighing 250-270 gm were randomly assigned to four groups, each group contain 6 animals. Group I Vehicle group-Received 1% Gum acacia + distilled water p.o for 14 days, Group II Negative control group- Received Chlorpromazine 3mg/kg, i.p. (dissolved with 1% gum acacia in distilled water suspension), Group III Standard group - Received Chlorpromazine (3mg/kg/day), i.p. + Diclofenac (10mg/kg/day) p. o., Group IV treatment group- Received Chlorpromazine (3mg/kg/day) i.p. + 1,2,4-Triazin derivative of Diclofenac at dose of 30mg/kg, p. o. Parkinson’s disease (PD) was induced by intra peritoneal injection of chlorpromazine 3mg/kg, i. p (dissolved with 1% gum acacia in distilled water suspension) daily for a period of 14 days. The 1, 2, 4-Trianine analogue of diclofenac was synthesised and evaluated against chlorpromazine induced PD by monitoring in vivo behavioural paramerters like muscle coordination, cognitive performance, catalepsy activity, Biochemical estimation of SGPT, SGOT, ALP, Total bilirubin, urea, creatinie and brain antioxidant levels, Acetylcholine, dopamine. Changes were confirmed by Histopathological studies. Results:Molecular docking of 1, 2, 4- Triazin derivative of diclofenac, binding scores of designed ligand was 1-10 scores with D3 protein, DDC, AA2AR, MAPK and MAO-B enzymes ranging from -6.35 to -5.64 Kcal/mol, -6.86 to -5.81 Kcal/mol, -6.11 to -5.02, -8.67 to -4.63 Kcal/mol, and -10.25 to -6.76 Kcal/mol respectively. Treatment group shows significant increase the body weight, feed intake, Locomotion action, muscle coordination, cognitive performance and dopamine level, also decrease in muscle ...