Determination of Potential Antagonist from Alkaloids as an Alternative Treatment for Nicotine Dependence using In Silico Approach

Smoking is a common practice of recreational drug use. Smoking has been known for its adverse effects on both physical and mental health. Smoking also leads to nicotine dependence, which produces various deleterious effects on smokers. The latest data from WHO revealed that smoking is the leading cause of death due to non-communicable diseases. Smoking has unalived 8 million people worldwide, and this number keeps increasing, especially in low- to middle-income middle-income countries. Treatment for nicotine dependence has been widely developed and shown promising efficacy in inducing abstinence; however, this utilization remains low due to limited treatment options. Hence, providing a new alternative for smoking cessation to give a new treatment option could help achieve cessation success. This study aims to determine the lead compound from natural alkaloids that could act as an antagonist towards nicotinic acetylcholine receptors (nAChrs) using an in silico approach. The target receptor nicotinic acetylcholine receptor (nAChRs) subtype α4β2 is one of the target receptors responsible for the occurrence of nicotine dependence in humans. The experiment includes a virtual screening of potential nAChRs subtype α4β2 antagonist with Quantitative Structure-Activity Relationship (QSAR) analysis, molecular docking using Patchdock, VisualizationVisualization, and toxicity analysis. Six of 43 alkaloids showed good potential as antagonists based on the complementary geometry scores and binding potential.