Integration of SwissADME, Toxicity Prediction, and Docking Analyses in Halal-Oriented Drug Discovery from Marine Microorganisms
Keywords:
Marine microorganism, Computational drug discovery, ADME, Protox, Halal-pharmaceuticalAbstract
Marine-derived microorganisms constitute an important source of structurally distinctive metabolites with emerging relevance to halal-compliant antibacterial drug development. However, limited information on their pharmacokinetic properties, toxicity risks, and molecular mechanisms restricts their translational potential. This study evaluated five metabolites: Notoamide U (1), Aspergilide F (2), Notoamide I (3), a benzimidazole derivative (4), and a Branimycin B analogue (5), using integrated in silico approaches comprising absorption, distribution, metabolism, excretion (ADME) prediction, toxicity modeling, as well as molecular docking against the bacterial division protein FtsZ. ADME analysis revealed moderate oral bioavailability across all compounds, with the compounds 1 and 3 showing the most favorable combination of gastrointestinal absorption, physicochemical properties, and metabolic behavior. Toxicity predictions placed the metabolites within toxicity classes 2–5, with LD50 values ranging from 7 to 2287 mg/kg. No hepatotoxicity or carcinogenicity was detected, although the benzimidazole derivative demonstrated cytotoxic potential and the compound 5 exhibited high acute toxicity. Docking results indicated binding affinities of –4.92 to –8.08 kcal/mol, the compound 4 showed the strongest interaction with FtsZ, while compound 1 displayed the most promising profile among natural metabolites. Overall, the findings highlight compounds 1 and 3 as strong candidates for further optimization and validation. These results emphasize the potential of marine microbial metabolites as halal-compatible antibacterial lead compounds.References
[1] C. Ragozzino et al., ‘Last Decade Insights in Exploiting Marine Microorganisms as Sources of New Bioactive Natural Products’, Marine Drugs, vol. 23, no. 3, p. 116, Mar. 2025, doi: 10.3390/md23030116.
[2] H. R. El-Seedi et al., ‘Marine natural products as a source of novel anticancer drugs: an updated review (2019–2023)’, Nat. Prod. Bioprospect., vol. 15, no. 1, p. 13, Jan. 2025, doi: 10.1007/s13659-024-00493-5.
[3] H. Chellapandian, S. Jeyachandran, K. Park, and I. Kwak, ‘Marine-Derived Functional Biomaterials: Advancements in Biomedicine and Drug Delivery Applications’, Natural Product Communications, vol. 20, no. 6, p. 1934578X241302009, June 2025, doi: 10.1177/1934578X241302009.
[4] M. Stielow, A. Witczyńska, N. Kubryń, Ł. Fijałkowski, J. Nowaczyk, and A. Nowaczyk, ‘The Bioavailability of Drugs—The Current State of Knowledge’, Molecules, vol. 28, no. 24, p. 8038, Jan. 2023, doi: 10.3390/molecules28248038.
[5] Z. Huang, Z. Xiao, C. Ao, L. Guan, and L. Yu, ‘Computational approaches for predicting drug-disease associations: a comprehensive review’, Front. Comput. Sci., vol. 19, no. 5, p. 195909, Nov. 2024, doi: 10.1007/s11704-024-40072-y.
[6] R. Ancuceanu, B. E. Lascu, D. Drăgănescu, and M. Dinu, ‘In Silico ADME Methods Used in the Evaluation of Natural Products’, Pharmaceutics, vol. 17, no. 8, p. 1002, Aug. 2025, doi: 10.3390/pharmaceutics17081002.
[7] P. Lancia, M. Louazzani, L. Gros, J. Ginestar, E. Fioravanzo, and A. Baleydier, ‘Overview of In Silico Tools to Evaluate Human Health Toxicity, Ecotoxicity, and Toxicokinetic Profiles in the Hazard Assessment of Chemicals Used in Cosmetics’, Chem. Res. Toxicol., vol. 38, no. 10, pp. 1652–1680, Oct. 2025, doi: 10.1021/acs.chemrestox.4c00534.
[8] D. Giordano, C. Biancaniello, M. A. Argenio, and A. Facchiano, ‘Drug Design by Pharmacophore and Virtual Screening Approach’, Pharmaceuticals, vol. 15, no. 5, p. 646, May 2022, doi: 10.3390/ph15050646.
[9] J. Alzeer, ‘Lifestylopathy and Ethical Pharmaceuticals: A Halalopathy Perspective’, Medical Research Archives, vol. 13, no. 3, Mar. 2025, doi: 10.18103/mra.v13i3.6384.
[10] T. S. Aung, W. Jasman, J. Alesandra, H. N. Johar, N. Hidayati, and M. F. Ruslan, ‘Halal practices for responsible production and consumption towards sustainable future’, Halal Studies and Society, vol. 2, no. 1, pp. 1–3, Jan. 2025, doi: 10.29244/hass.2.1.1-3.
[11] P. Selvakumar, R. Dahiya, N. Malik, T. C. Manjunath, M. Sharma, and R. Kumar, ‘Halal Cosmetics and Pharmaceutics’, in Exploring the Halal Industry and Its Business Ecosystem Prospects, IGI Global Scientific Publishing, 2025, pp. 189–210. doi: 10.4018/979-8-3693-8618-7.ch009.
[12] N. M. Mazuki and A. Bhari, ‘ADDRESSING CHALLENGES AND ISSUES IN ESTABLISHING A HALAL PHARMACY FOR MUSLIM COMMUNITIES’, Quantum Journal of Social Sciences and Humanities, vol. 5, no. 6, pp. 221–227, Dec. 2024, doi: 10.55197/qjssh.v5i6.498.
[13] A. Setiawan et al., ‘Solid State Fermentation of Shrimp Shell Waste Using Pseudonocardia carboxydivorans 18A13O1 to Produce Bioactive Metabolites’, Fermentation, vol. 7, no. 4, p. 247, Oct. 2021, doi: 10.3390/fermentation7040247.
[14] A. Setiawan, R. Lutfiah, W. A. Setiawan, J. Hendri, and M. Arai, ‘Antibacterial activity of EtOAc extract from marine-derived fungus Aspergillus nomiae A12-RF against clinical pathogen bacteria, Staphylococcus aureus’, vol. 15, no. 3, 2022.
[15] A. Setiawan et al., ‘Fungicide Activity of Culture Extract from Kocuria palustris 19C38A1 against Fusarium oxysporum’, JoF, vol. 8, no. 3, p. 280, Mar. 2022, doi: 10.3390/jof8030280.
[16] A. Daina, O. Michielin, and V. Zoete, ‘SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules’, Sci Rep, vol. 7, no. 1, p. 42717, Mar. 2017, doi: 10.1038/srep42717.
[17] P. Banerjee, A. O. Eckert, A. K. Schrey, and R. Preissner, ‘ProTox-II: a webserver for the prediction of toxicity of chemicals’, Nucleic Acids Res, vol. 46, no. W1, pp. W257–W263, July 2018, doi: 10.1093/nar/gky318.
[18] S. Azimi, B. Mohammadi, S. Babadoust, and E. Vessally, ‘In Silico study and design of some new potent threonine tyrosine kinase inhibitors using molecular docking simulation’, Molecular Simulation, Mar. 2023, Accessed: Nov. 08, 2025. [Online]. Available: https://www.tandfonline.com/doi/abs/10.1080/08927022.2023.2172192
[19] I. E. Vishnyakov and S. N. Borchsenius, ‘FtsZ and bacterial cell division’, Cell Tiss. Biol., vol. 1, no. 3, pp. 206–214, June 2007, doi: 10.1134/S1990519X07030029.
[20] A. Roy and A. Anbarasu, ‘Unveiling Berberine analogues as potential inhibitors of Escherichia coli FtsZ through machine learning molecular docking and molecular dynamics approach’, Sci Rep, vol. 15, no. 1, p. 14668, Apr. 2025, doi: 10.1038/s41598-025-98835-x.
[21] K. Kumar et al., ‘Novel Trisubstituted Benzimidazoles, Targeting Mtb FtsZ, As A New Class of Antitubercular Agents’, J Med Chem, vol. 54, no. 1, pp. 374–381, Jan. 2011, doi: 10.1021/jm1012006.
[22] T. Li et al., ‘Identification of novel 4-substituted 7H-pyrrolo[2,3-d]pyrimidine derivatives as new FtsZ inhibitors: Bioactivity evaluation and computational simulation’, Bioorganic Chemistry, vol. 150, p. 107534, Sept. 2024, doi: 10.1016/j.bioorg.2024.107534.
[23] R. van der Lee et al., ‘Classification of Intrinsically Disordered Regions and Proteins’, Chem. Rev., vol. 114, no. 13, pp. 6589–6631, July 2014, doi: 10.1021/cr400525m.
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