eng Oriental Scientific Publishing Company Biosciences Biotechnology Research Asia 0973-1245 2026-03-30 23 1 264 279 10.13005/bbra/3496 58215 article Harshali Narayan Anap 1 Ajim Raju Patwekari 2 Gaurav Mohanrao Bhosale 2 Sapna Ashok Chavan 2 Pratiksha Bharat Talole 2 Rajashree Gangadhar Dighe 2 Department of Pharmaceutical Chemistry, Sitabai Thite college of Pharmacy; Shirur; Pune; Maharashtra; India. Department of Pharmaceutical Chemistry, Pravara Rural College of Pharmacy, Pravaranagar; Maharashtra; India. Tafenoquine (TF), a quinoline-derived antimalarial compound, had been utilized both as a chemoprophylactic agent and in combination therapies such as with artesunate. Despite its potent efficacy against Plasmodium falciparum, its clinical application had been restricted due to reports of neurotoxicity and adverse neuropsychiatric reactions. Previous computational investigations indicated that TF functioned as a dual cholinesterase inhibitor with a high affinity for protein targets, findings that were subsequently corroborated through in vitro enzymatic inhibition studies. Malaria continued to represent a significant global health challenge, particularly within tropical and subtropical regions, owing to the emergence of Plasmodium falciparum and Plasmodium vivax strains resistant to conventional antimalarial drugs. Targeting essential parasitic enzymes, including aspartic proteases, had been recognized as a promising strategy for discovering novel chemotherapeutic candidates. In the present study, an in silico molecular docking approach was employed to examine a series of Tafenoquine analogues as potential inhibitors of critical Plasmodium proteins. Among the fourteen designed derivatives, TF4A, TF8A, TF3A, and TF1A exhibited stronger binding affinities than the parent compound Tafenoquine, with docking energies of −8.1, −8.5, −8.0, and −8.2 kcal/mol, respectively. Additionally, ADMET evaluation and drug-likeness analyses demonstrated that these analogues possessed acceptable pharmacokinetic characteristics and conformed to Lipinski’s rule of five, suggesting good oral bioavailability and favorable physicochemical behavior. Collectively, the computational findings indicated that halogen-substituted Tafenoquine analogues, particularly TF8A and TF1A, established stable interactions within the catalytic pockets of target proteins and exhibited enhanced binding energies. Therefore, these derivatives could be considered as promising lead scaffolds for future antimalarial drug development. Nevertheless, further in vitro and in vivo investigations would be necessary to validate their efficacy, metabolic stability, and safety profiles. https://www.biotech-asia.org/vol23no1/in-silico-screening-and-molecular-dynamics-simulation-of-tafenoquine-derivatives-targeting-plasmodium-vivax-protease-pdb-id-3ihz/ ADMET Prediction; 1-Click Docking software; Discovery Studio; PDB ID 3IHZ; Plasmodium Vivax; Tafenoquine TF