Viski Fitri Hendrawan, Epy Muhammad Luqman, Rimayanti Rimayanti, Widjiati Widjiati, Iwan Sahrial Hamid, Moh. Anam Al Arif, Hani Plumeriastuti, Tri Wahyu Suprayogi
Nigella sativa is widely recognized for its anti-inflammatory, antioxidant, and immunomodulatory activities; yet, a systematic in silico assessment of its major phytocompounds against inflammation-and apoptosis-related targets remains limited. This study employed an integrated bioinformatics and molecular docking approach to evaluate the drug-likeness, toxicity, predicted bioactivity, and protein ligand interactions of four key Nigella sativa constituents: thymoquinone, thymohydroquinone, nigellidine, and nigellicine. Druglikeness and pharmacokinetic properties were analyzed using SwissADME, toxicity was predicted through ProTox 3.0, and bioactivity profiles were estimated using PASS Online. Molecular docking simulations were conducted using AutoDock Vina targeting TNF-α (PDB: 2AZ5) and caspase-3 (PDB: 3KJF), followed by interaction visualization in Discovery Studio 2024. All compounds satisfied Lipinski’s Rule of Five, suggesting good oral drug-likeness, with nigellicine showing the highest predicted bioavailability score (0.85). Thymoquinone and thymohydroquinone demonstrated the safest toxicity profiles, whereas nigellidine and nigellicine indicated possible organ-specific risks. Docking results showed that nigellidine exhibited the strongest binding affinity to TNF-α (–8.2 kcal/mol) and caspase-3 (–6.7 kcal/mol), forming stable interactions with key active-site residues. Overall, these findings highlight nigellidine and nigellicine as promising dual-target inhibitors with potential therapeutic relevance for inflammation and apoptosis-associated conditions. This work supports the development of natural bioactive compounds and aligns with Sustainable Development Goal 3 (Good health and well-being). © 2026 by SPC (Sami Publishing Company), Asian Journal of Green Chemistry.
Doctoral Program of Veterinary Science, Faculty of Veterinary Medicine, Universitas Airlangga, East Java, Surabaya, 60115, Indonesia; Division of Veterinary Reproduction, Faculty of Veterinary Medicine, Universitas Brawijaya, Malang, Indonesia; Division of Veterinary Anatomy, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia; Division of Veterinary Reproduction, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Veterinary Medicine Science, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia; Division of Veterinary Pharmacology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia; Division of Veterinary Science (Animal Nutrition), Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia; Division of Veterinary Pathology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia
