Anthelmintic Potential of Abietic Acid: Integrated In Silico, MolecularDynamics, and In Vitro Evaluation Targeting β-Tubulin in Pheretimaposthuma

Introduction: Helminthiasis poses a significant global health problem, particularly in tropical and subtropical regions. The limitations of currently available drugs further underscore the urgent need to identify new therapeutic candidates. Materials and Methods: An investigation into the anthelmintic potential of Abietic Acid (ABI) via in silico and in vitro methods was performed. Density Functional Theory (DFT) calculations, molecular docking studies, and Molecular Dynamics (MD) simulations were carried out. The in vitro anthelmintic activity was tested using the Pheretima posthuma model. ADMET (absorption, distribution, metabolism, excretion, and toxicity) assessments were conducted to determine the drug-like properties of the compound. Results: DFT revealed that ABI has a greater HOMO (Highest Occupied Molecular Orbital)- LUMO (Lowest Unoccupied Molecular Orbital) gap and hardness than albendazole (ALB). Molecular docking revealed a greater binding affinity of ABI (-7.1 kcal/mol) for β-tubulin than for ALB (-6.8 kcal/mol). The MD simulations suggested the stability of the ABI-β-tubulin complex. In vitro studies revealed that ABI exhibited dose-dependent anthelmintic activity, with paralysis times ranging from 15.23±0.78 to 6.87±0.67 min at concentrations ranging from 5-20 mg/ml. Discussion: The promising anthelmintic potential of ABI is like that of albendazole (ALB) at higher concentrations. Although the ADMET prediction revealed good drug-like properties for ABI, it still requires careful monitoring because of the toxicity prediction. Conclusion: ABI can be considered a potential anthelmintic candidate; however, further in vivo evaluations of its efficacy and safety are needed. This natural compound-based approach may constitute a significant step in the fight against helminthiasis.