IN SILICO ANALYSIS OF ANTIFUNGAL POTENTIAL, PHYSICOCHEMICAL PROPERTIES, DRUG-LIKENESS, AND TOXICITY OF BIOACTIVE COMPOUNDS OF Cannabis spp. AS BIOFUNGICIDE CANDIDATES FOR CONTROLLING FUNGAL DISEASES IN OIL PALM PLANTS
ANALISIS IN SILICO POTENSI ANTIFUNGI, SIFAT FISIKOKIMIA, DRUG-LIKENESS, DAN TOKSISITAS SENYAWA BIOAKTIF Cannabis spp. SEBAGAI KANDIDAT BIOFUNGISIDA UNTUK PENGENDALIAN PENYAKIT JAMUR PADA TANAMAN KELAPA SAWIT
DOI:
https://doi.org/10.71275/roce.v3i2.209Keywords:
Cannabis sativa, Antifungal activity, Biofungicide, Cannabinoids, Flavonoids, Drug-likeness, PKCSM, Oil palm diseaseAbstract
This study aimed to evaluate the antifungal potential, physicochemical properties, drug-likeness characteristics, and toxicity profiles of bioactive compounds from Cannabis plants using in silico approaches. The analyses were conducted using PASS Online, SwissADME, and PKCSM platforms to identify potential natural antifungal agents for controlling fungal diseases in oil palm plants. PASS analysis demonstrated that several compounds exhibited strong antifungal activity, particularly glycoside flavonoids and cannabinoid compounds. Flavosativaside, orientin 7-glucoside, and flavocannabiside showed the highest Probability of Active (Pa) values, indicating promising antifungal potential. Cannabinoid compounds such as cannabidiol (CBD), cannabigerolic acid (CBGA), and tetrahydrocannabivarin also displayed considerable antifungal activity due to their lipophilic properties, which facilitate penetration into fungal cell membranes. SwissADME analysis revealed that most compounds possessed favorable physicochemical and pharmacokinetic characteristics, including acceptable lipophilicity, water solubility, and bioavailability. Several flavonoids and cannabinoids fulfilled major drug-likeness criteria, including Lipinski, Ghose, Veber, Egan, and Muegge rules, suggesting good potential for biological interaction and absorption. Simple flavonoids and cannabinoids exhibited more balanced polarity and membrane permeability than glycoside flavonoids, which generally had higher molecular weights and polar surface areas. PKCSM toxicity prediction indicated that most compounds were non-mutagenic and non-hepatotoxic, although several showed potential mutagenic or hepatotoxic effects that warrant further investigation. Environmental toxicity analysis suggested that most compounds exhibited low to moderate ecological toxicity, supporting their potential application as environmentally friendly biofungicides. Overall, the results indicate that Cannabis-derived compounds possess significant potential as natural antifungal agents for controlling fungal diseases in oil palm plantations. The integration of PASS, SwissADME, and PKCSM analyses provides an efficient preliminary screening strategy to identify effective and safe bioactive compounds before further in vitro and in vivo studies.
Downloads
References
A, A. D., B, S., & S, V. (2026). In silico structure-based multi-targeted molecular docking analysis of ginkgo biloba phytocompounds against Alzheimer's disease associated proteins. In Silico Research in Biomedicine, 2, 100411. https://doi.org/https://doi.org/10.1016/j.insi.2026.100411
Aburagaegah, S. (2025). The Critical Role of In Silico Laboratory Approaches in Pharmaceutical Microbiology and Novel Drug Discovery: A Review Study. Attahadi Medical Journal, 201–205. https://doi.org/10.69667/amj.25302
Al Aboody, M. S., & Mickymaray, S. (2020). Anti-Fungal Efficacy and Mechanisms of Flavonoids. Antibiotics, 9(2). https://doi.org/10.3390/antibiotics9020045
Alengebawy, A., Abdelkhalek, S. T., Qureshi, S. R., & Wang, M.-Q. (2021). Heavy Metals and Pesticides Toxicity in Agricultural Soil and Plants: Ecological Risks and Human Health Implications. Toxics, 9(3). https://doi.org/10.3390/toxics9030042
Benatar, G. V., Nurhayati, Y., & Ridwan, N. F. (2024). In silico toxicity evaluation of plant-based biofungicides and their docking properties with cutinase protein of Colletotrichum gloeosporioides, the pathogen of mango anthracnose. Authorea, 2024(0901). https://doi.org/10.22541/au.172515783.32130789/v1
Bridgeman, M. B., & Abazia, D. T. (2017). Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P & T : A Peer-Reviewed Journal for Formulary Management, 42(3), 180–188.
Caminero Gomes Soares, A., Marques Sousa, G. H., Calil, R. L., & Goulart Trossini, G. H. (2023). Absorption matters: A closer look at popular oral bioavailability rules for drug approvals. Molecular Informatics, 42(11), e202300115. https://doi.org/https://doi.org/10.1002/minf.202300115
Cenobio-Galindo, A. de J., Hernández-Fuentes, A. D., González-Lemus, U., Zaldívar-Ortega, A. K., González-Montiel, L., Madariaga-Navarrete, A., & Hernández-Soto, I. (2024). Biofungicides Based on Plant Extracts: On the Road to Organic Farming. International Journal of Molecular Sciences, 25(13). https://doi.org/10.3390/ijms25136879
Chen, Z., Świsłocka, R., Choińska, R., Marszałek, K., Dąbrowska, A., Lewandowski, W., & Lewandowska, H. (2024). Exploring the Correlation Between the Molecular Structure and Biological Activities of Metal–Phenolic Compound Complexes: Research and Description of the Role of Metal Ions in Improving the Antioxidant Activities of Phenolic Compounds. International Journal of Molecular Sciences, 25(21). https://doi.org/10.3390/ijms252111775
Coelho, M. J., Araújo, M. D., Carvalho, M., Cardoso, I. L., Manso, M. C., & Pina, C. (2025). Antimicrobial Potential of Cannabinoids: A Scoping Review of the Past 5 Years. Microorganisms, 13(2). https://doi.org/10.3390/microorganisms13020325
Durrani, A. K., Khalid, M., Raza, A., ul Rasool, I. F., Khalid, W., Akhtar, M. N., Khan, A. A., Abdullah, Z., & Khadijah, B. (2024). Clinical improvement, toxicity and future prospects of β-sitosterol: a review. CyTA - Journal of Food, 22(1), 2337886. https://doi.org/10.1080/19476337.2024.2337886
Esmaeili, A., Saleh, I., & Abu-Dieyeh, M. H. (2025). Antifungal potential of plant-based extracts against Candida species: values, safety concerns, and possible applications. Phytochemistry Reviews, 24(6), 5801–5844. https://doi.org/10.1007/s11101-025-10093-x
Goel, R., Singh, D. D., Lagunin, A., & Poroikov, V. (2011). PASS-assisted exploration of new therapeutic potential of natural products. Medicinal Chemistry Research, 20, 1509–1514. https://doi.org/10.1007/s00044-010-9398-y
Górniak, I., Bartoszewski, R., & Króliczewski, J. (2019). Comprehensive review of antimicrobial activities of plant flavonoids. Phytochemistry Reviews, 18(1), 241–272. https://doi.org/10.1007/s11101-018-9591-z
Hu, L., Luo, Y., Yang, J., & Cheng, C. (2025). Botanical Flavonoids: Efficacy, Absorption, Metabolism and Advanced Pharmaceutical Technology for Improving Bioavailability. Molecules, 30(5). https://doi.org/10.3390/molecules30051184
Kırboğa, K. K., Karim, A., Küçüksille, E. U., Rudrapal, M., Khan, J., Achar, R. R., Silina, E., Manturova, N., & Stupin, V. (2024). Exploring the antifungal potential of Cannabis sativa-derived stilbenoids and cannabinoids against novel targets through in silico protein interaction profiling. Frontiers in Chemistry, 12, 1515424. https://doi.org/10.3389/fchem.2024.1515424
Leeson, P. D., Bento, A. P., Gaulton, A., Hersey, A., Manners, E. J., Radoux, C. J., & Leach, A. R. (2021). Target-Based Evaluation of “Drug-Like” Properties and Ligand Efficiencies. Journal of Medicinal Chemistry, 64(11), 7210–7230. https://doi.org/10.1021/acs.jmedchem.1c00416
Lombardo, F., Desai, P. V, Arimoto, R., Desino, K. E., Fischer, H., Keefer, C. E., Petersson, C., Winiwarter, S., & Broccatelli, F. (2017). In Silico Absorption, Distribution, Metabolism, Excretion, and Pharmacokinetics (ADME-PK): Utility and Best Practices. An Industry Perspective from the International Consortium for Innovation through Quality in Pharmaceutical Development. Journal of Medicinal Chemistry, 60(22), 9097–9113. https://doi.org/10.1021/acs.jmedchem.7b00487
Mao, F., Ni, W., Xu, X., Wang, H., Wang, J., Ji, M., & Li, J. (2016). Chemical Structure-Related Drug-Like Criteria of Global Approved Drugs. Molecules (Basel, Switzerland), 21(1), 75. https://doi.org/10.3390/molecules21010075
Mitra, S., Saran, R. K., Srivastava, S., & Rensing, C. (2024). Pesticides in the environment: Degradation routes, pesticide transformation products and ecotoxicological considerations. Science of The Total Environment, 935, 173026. https://doi.org/https://doi.org/10.1016/j.scitotenv.2024.173026
Mok, Z. H. (2024). The effect of particle size on drug bioavailability in various parts of the body. Pharmaceutical Science Advances, 2, 100031. https://doi.org/https://doi.org/10.1016/j.pscia.2023.100031
Moshkov, N., Becker, T., Yang, K., Horvath, P., Dancik, V., Wagner, B. K., Clemons, P. A., Singh, S., Carpenter, A. E., & Caicedo, J. C. (2023). Predicting compound activity from phenotypic profiles and chemical structures. Nature Communications, 14(1), 1967. https://doi.org/10.1038/s41467-023-37570-1
Mota Fernandes, C., Dasilva, D., Haranahalli, K., McCarthy, J. B., Mallamo, J., Ojima, I., & Del Poeta, M. (2021). The Future of Antifungal Drug Therapy: Novel Compounds and Targets. Antimicrobial Agents and Chemotherapy, 65(2). https://doi.org/10.1128/AAC.01719-20
Mswahili, M. E., & Jeong, Y.-S. (2024). Transformer-based models for chemical SMILES representation: A comprehensive literature review. Heliyon, 10(20), e39038. https://doi.org/https://doi.org/10.1016/j.heliyon.2024.e39038
Pirzada, A. S., Khan, H., Alam, W., Darwish, H. W., Elhenawy, A. A., Kuznetsov, A., & Daglia, M. (2024). Physicochemical properties, pharmacokinetic studies, DFT approach, and antioxidant activity of nitro and chloro indolinone derivatives. Frontiers in Chemistry, Volume 12-2024. https://doi.org/10.3389/fchem.2024.1360719
Simei, J. L. Q., Souza, J. D. R., Pedrazzi, J. F., Guimarães, F. S., Campos, A. C., Zuardi, A., Hallak, J. E. C., & Crippa, J. A. S. (2024). Research and Clinical Practice Involving the Use of Cannabis Products, with Emphasis on Cannabidiol: A Narrative Review. Pharmaceuticals (Basel, Switzerland), 17(12). https://doi.org/10.3390/ph17121644
Sliwoski, G., Kothiwale, S., Meiler, J., & Lowe, E. W. J. (2014). Computational methods in drug discovery. Pharmacological Reviews, 66(1), 334–395. https://doi.org/10.1124/pr.112.007336
Tang, S., Wang, B., Liu, X., Xi, W., Yue, Y., Tan, X., Bai, J., & Huang, L. (2025). Structural insights and biological activities of flavonoids: Implications for novel applications. Food Frontiers, 6(1), 218–247. https://doi.org/https://doi.org/10.1002/fft2.494
Tariq, L., Bhat, B. A., Hamdani, S. S., & Mir, R. A. (2021). Phytochemistry, Pharmacology and Toxicity of Medicinal Plants BT - Medicinal and Aromatic Plants: Healthcare and Industrial Applications (T. Aftab & K. R. Hakeem, Eds.; pp. 217–240). Springer International Publishing. https://doi.org/10.1007/978-3-030-58975-2_8
Tian, F., Woo, S. Y., Lee, S. Y., Park, S. B., Zheng, Y., & Chun, H. S. (2022). Antifungal Activity of Essential Oil and Plant-Derived Natural Compounds against Aspergillus flavus. Antibiotics (Basel, Switzerland), 11(12). https://doi.org/10.3390/antibiotics11121727
Urs, A. R., Ganesan Selvi, V., Sreekumar, A., Sudarsan, A., Murthy, P. V, Reddy A H, M., & Manokaran, S. (2026). Benchmarking web-based in-silico toxicity prediction tools using gold-standard datasets across five key endpoints. Discover Applied Sciences, 8(3), 323. https://doi.org/10.1007/s42452-026-08308-7
Volkova, T. V., & Perlovich, G. L. (2023). Permeability of New Antifungal Fluconazole Derivatives through a Lipophilic Membrane: Experiment and Modeling. Molecules, 28(1). https://doi.org/10.3390/molecules28010389
Wardecki, D., Dołowy, M., & Bober-Majnusz, K. (2023). Assessment of Lipophilicity Parameters of Antimicrobial and Immunosuppressive Compounds. Molecules (Basel, Switzerland), 28(6). https://doi.org/10.3390/molecules28062820
Wu, K., Kwon, S. H., Zhou, X., Fuller, C., Wang, X., Vadgama, J., & Wu, Y. (2024). Overcoming Challenges in Small-Molecule Drug Bioavailability: A Review of Key Factors and Approaches. International Journal of Molecular Sciences, 25(23). https://doi.org/10.3390/ijms252313121
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Okduartus Ryan, Muhammad Pirmansyah, Togu Pasternar Manik, seto kuncoro jati, Glenn Augusthio, uswatun nurul khoiriah, dodi iskandar (Author)
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
