Ligand and Structure-Based Hybrid Screening for Anti-Parkinson Agents and their Pharmacological Evaluation

Abstract

The behavioral and biochemical antiparkinson effect of 7-hydroxyflavone (7-HF) was evaluated by using virtual screening with an e-pharmacophore and shape-based screening approach, and the compound was screened by using the Sigma Aldrich compound library. Screened hits were filtered based on Lipinski’s rule, absorption, distribution,metabolism,elimination, (software for evaluation) (ADME), and toxicity parameters. The best scoring hit, 7-hydroxy 2 phenyl-4H-chromen-4-one, i.e., 7-HF was selected based on shape similarity (> 0.7), g-score, and conserved interactions. Toxicity assessment of retrieved hits was carried out by Osiris and Lazar programs. This study aims to obtain some potential hits, against various antiparkinson category from reported literature and available online resources, and validate their potency by in vivo, in vitro methods. Reserpine 5 mg/kg produces Parkinson’s like condition by depleting presynaptic catecholamines, particularly dopamine through the process of degranulation of storage vesicles. 7-HF 25, 50, and 100 mg/kg was used as a test compound. Syndopa 275 mg/kg was used as a standard drug. The results demonstrate that treatment with 7-HF improved the total locomotor activity and muscular coordination in the rotarod test. In the open field test, enhanced rearing, grooming duration of mobility, and gripping strength in the chimney test, while a decrease in cataleptic scores in the bar test. 7-HF significantly increases catalase, superoxide dismutase, and reduces glutathione level, while reduced the Malondialdehyde (MDA) level. The total protein concentration was also increased in 7-HF treated groups. The behavioral and biochemical results obtained from this study disclosed a definite neuroprotective role of 7-HF in a dose-dependent manner. It is also clear that 7-HF showed potent and effective antiparkinson activity in a similar way as standard. Interestingly, in behavioral and biochemical studies, 7-HF showed approximately equivalent effects as compared to syndopa.