1Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education &amp; Research, Ooty, The Nilgiris, Tamilnadu, India
2Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education &amp; Research Ooty, Nilgiris, Tamilnadu, India.
3Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research Ooty, Nilgiris, Tamilnadu, India.
4Department of Biotechnology, JSS College of Pharmacy, JSS Academy of Higher Education & Research Ooty, Nilgiris, Tamilnadu, India.
5Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
Since depression is a common mental illness that affects an estimated 5% of people worldwide, investigators are encouraged to develop effective antidepressants. Depletion of the neurotransmitters serotonin, norepinephrine, or dopamine in the central nervous system is one of the pathophysiologies of depression. The neurotransmitter serotonin has drawn the most attention in relation to depression. As per research 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) when administered as a single inhalation of vapour from dried toad secretion, is found to have higher life satisfaction and convergent thinking, higher ratings of mindfulness, and lower ratings of depression, anxiety, and stress. It lowers stress biomarkers (such cortisol). The current study aims to look at 5-MeO-DMT analogues as possible antidepressants. We used 70,000 5-MeO-DMT analogues that were sketched using Marvin to conduct a high throughput virtual screening (HTVS) method in hopes of finding potential 5-MeO-DMT analogues against the 5-HT1AR (7E2Y.pdb) as an agonist. The prediction of the analogue-protein interaction and the evaluation of the binding affinity are accomplished employing molecular docking. The Glide XP docking data indicated that a total of 21 compounds had Glide gscores ranging from -11.41 to -6.53 kcal/mol. When compared to the standard 5-MeO-DMT with binding affinity of -7.75 kcal/mol, 14 compounds showed better binding affinity. Further MM-GBSA indicated a binding free energy range of -63.55 to -35.37 kcal/mol. Through ligand binding interactions with Asp116, Phe361, Phe362, Ser190, Ser199, Val117, Trp358, Ala365, Pro369, Ile189, Tyr195, Ala203, Ile167, Tyr390, Cys120, Trp358, Val364, Ala365, and Leu368 these complexes were stabilized, according to the molecular dynamics simulation of 20453/7E2Y in 100ns.