MOLECULAR DOCKING STUDIES OF PHYTOCHEMICALS OF VITEX NEGUNDO (L) AGAINST ADENOSINE A1 RECEPTOR AS THERAPEUTIC TARGET IN CARDIOVASCULAR DISEASES

Recent days, Ayurveda medicine is becoming one of the best alternatives for the modern medicines for effective control of Cardiovascular disease (CVD) due to their limited side effects and availability to a common man. Vitex negundo (L.) is a woody, large aromatic shrub growing to a small tree, which thrives in humid places or along water courses in wastelands, mixed open forests and found to occur widely in India, Afghanistan, Pakistan, Sri Lanka, Thailand, Malaysia, eastern Africa and Madagascar. The study evaluates a few selected phytochemicals (5,3′-dihydroxy-7,8,4′-trimethoxyflavanone; 5,3′-dihydroxy -6,7,4′trimethoxyflavanone; 5-hydroxy-7,4'dimethoxyflavone; 5,3'-dihydroxy-7,8,4'-trimethoxyflavanone; betulinic acid, ursolic acid; n-hentriacontanol; β-sitosterol) present in V. negundo plant leaves based on their capacity to bind and inhibit Adenosine A1 receptor of CVD using computational methods. Using the crystal structure of Adenosine A1 receptor from the Protein Data Bank, possible binding sites of Adenosine receptor were evaluated with CASTP server. Simultaneously, Molecular docking was performed using the GOLD (Genetic Optimization of Ligand Docking) software, to study the binding orientation of compounds to the Adenosine receptor. The efficiency and drug-likeness of various plant compounds were identified by using pre-ADMET software. In this study, all docked compounds were found to have interaction between an oxygen atom of the compounds and Adenosine receptor. In the binding pocket, common H-bonding interactions were formed between all docked compounds and GLY 135, GLN 137, GLN 140, HIS 143, GLU 145, GLN 145, GLN 207, ASP 209, HIS 232, THR 300, and HIS 311. The docking results agreed well with the observed in vitro data, which showed that the Adenosine receptor inhibitory activity of 5-hydroxy-7,4'dimethoxyflavone was higher than those of other compounds.