Structure-Based Investigation of Chromolaena odorata Compounds Against Key Proteins Implicated in Obesity Using Molecular Docking Approaches

Obesity remains a significant global health burden, contributing to a spectrum of metabolic disorders including cardiovascular diseases, type 2 diabetes, and dyslipidemia. Despite the availability of pharmacological interventions, issues such as adverse effects, high cost, and long-term inefficacy necessitate the search for safer, plant-based alternatives. This study aimed to evaluate the anti-obesity potential of phytochemicals derived from Chromolaena odorata (commonly known as devil weed) through theoretical and molecular docking approaches against two obesity-related protein targets: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and Fat Mass and Obesity-associated protein (FTO). A total of 68 bioactive compounds were retrieved from literature and docked using PyRx and Discovery Studio. Binding affinities were analyzed, and the molecular interactions were visualized using 2D diagrams to identify key interacting residues. The top compounds—Naringin, Curcumin, Rutin, and Catechin—exhibited higher binding affinities than standard anti-obesity drugs such as Orlistat and Phentermine, with Naringin recording -9.8 kcal/mol against FTO and -9.3 kcal/mol against HMG-CoA reductase. These compounds interacted with critical active site residues such as ARG261, GLU234, TYR108, and HIS231, indicating strong binding potential. Further assessment of pharmacokinetic properties and drug-likeness using ADMETLab 2.0 and Lipinski’s rule of five revealed that most lead compounds exhibited favorable oral bioavailability, low toxicity, and acceptable clearance rates. The 2D structural analysis highlighted the importance of hydroxyl-rich polyphenolic and glycosylated frameworks in stabilizing ligand-protein interactions. This study concludes that C. odorata contains promising phytochemical candidates for anti-obesity drug development. The findings provide a scientific foundation for further in vitro and in vivo studies to validate the therapeutic efficacy and safety of these compounds.