Molegro Virtual Docker-Based Prediction of Rhodomyrtus tomentosa Metabolites Targeting Ribonucleotide Reductase as Potential Anticancer Agents
Abstract
The increasing number of cancer cases has prompted the search for new drug candidates from natural ingredients, particularly plant-derived compounds considered safer and more effective. Rhodomyrtus tomentosa (Aiton) Hassk. contains various metabolites responsible for various biological activities. This study aimed to predict the anticancer potential of R. tomentosa metabolites against the Ribonucleotide Reductase (RNR) enzyme using an in silico approach. The RNR protein structure (PDB ID: 2WGH) was obtained from the RCSB Protein Data Bank. Molecular docking was performed on 25 compounds previously reported in the literature as metabolites of R. tomentosa using Molegro Virtual Docker (MVD) version 7.0 to evaluate ligand-receptor binding affinity based on MolDock Score values using a validated docking protocol (RMSD≤2.0 Å), followed by interaction analysis and pharmacokinetic evaluation using ADMET parameters. The results indicated that most compounds exhibited favorable binding affinities toward RNR, as reflected by negative MolDock Score values. Rhodomyrtosone B (−137.144 kcal/ mol) showed the best binding affinity, followed by Malvidin-3-glucoside (−135.173 kcal/ mol), Delphinidin-3-galactoside (-132.359 kcal/mol), Rhodomyrtosone I (−130.004 kcal/ mol), and Cyanidin-3-galactoside (-127.741 kcal/mol). Interaction analysis revealed stable interactions with key amino acid residues (Arg256, Asp226, and Ser269) through hydrogen bonding, hydrophobic, and electrostatic interactions. ADMET analysis indicated variability in pharmacokinetic properties, including absorption, distribution, metabolism, and toxicity. In conclusion, Rhodomyrtosone B has potential as a natural product-based anticancer agent targeting RNR, providing a basis for further in vitro and in vivo studies.
Keywords: anticancer, Rhodomyrtus tomentosa, molecular docking, Ribonucleotide Reductase; in silico.
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Chen, D., Xu, F., Zhang, P., Deng, J., Sun, H., Wen, X., and Liu, J., 2017, Practical synthesis of a-Amyrin, b-Amyrin, and lupeol: The potential natural inhibitors of human oxidosqualene cyclase, ARCH PHARM Archiv Der Pharmazie, 350(12), 1–9. CrossRef
Chen, G., Luo, Y., Warncke, K., Sun, Y., Yu, D.S., Fu, H., et al., 2019, Acetylation regulates ribonucleotide reductase activity and cancer cell growth, Nature Communications, 10(1), 3213. CrossRef
Dachriyanus, Fahmi, R., Sargent, M.V., Skelton, B.W. and White, A.H., 2004, 5-Hy¬droxy-3,3000,4000,5000,7-pentamethoxyfla¬vone (combretol), Acta Crystallographica, 60(1), 86–88.
Fairman, J.W., Wijerathna, S.R., Ahmad, M.F., Xu, H., Nakano, R., Jha, S., et al., 2011, Structural basis for allosteric regulation of human ribonucleotide reductase by nucleotide-induced oligomerization, Nature Structural and Molecular Biology, 18(3), 316–322. CrossRef
Ferlay, J., Rebecca, M.E. and Mph, L.S., 2024, Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, International Agency for Research on Cancer/World Health Organization, 74(3), 229–263. CrossRef
Fu, L., Shi, S., Yi, J., Wang, N., He, Y., Wu, Z., et al., 2024, ADMETlab 3.0: an updated comprehensive online ADMET prediction platform enhanced with broader coverage, improved performance, API functionality and decision support, Nucleic Acid Research, 52(W1), W422-W431. CrossRef
Fujiati, F., Haryati, H., Joharman, J., and Utami, S.W., 2022, In vitro metabolite profiling and anti-inflammatory activities of Rhodomyrtus tomentosa with red blood cell membrane stabilization methods, Reports of Biochemistry & Molecular Biology, 11(3), 503–510. CrossRef
Gu, Y., Yang, R., Zhang, Y., Guo, M., Takehiro, K., Zhan, M., et al., 2025, Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer, Molecular Biomedicine, 6(1), 2. CrossRef
Hadi, S. and Nastiti, K., 2023, Activity predication of Rhodomyrtus tomentosa (Aiton) Hassk against ACE1 inhibitors, Science Midwifery, 11(2), 348– 355. CrossRef
Huff, S.E., Winter, J.M., and Dealwis, C.G., 2022, Inhibitors of the cancer target ribonucleotide reductase, past and present, Biomolecules, 12(6), 815. CrossRef
Idris, M., Purnomo, A.S., Martak, F., Kim, Y-U., and Fatmawati, S., 2023, Chemical compounds and pharmaceutical properties of Rhodomyrtus to mentosa: A traditional medicinal herb from South Kalimantan, Indonesia, Journal of Hunan University Natural Sciences, 50(8), 100–123. CrossRef
Idris, M., Sukandar, E.R., Purnomo, A.S., Martak, F. and Fatmawati, S., 2022, Antidiabetic, cytotoxic and antioxidant activities of Rhodomyrtus tomentosa leaf extracts, RSC Advances, 12(39), 25697–25710. CrossRef
Islam, M.O., Bacchetti, T., and Ferretti, G., 2019, Alterations of antioxidant enzymes and biomarkers of nitro-oxidative stress in tissues of bladder cancer, Hindawi Oxidative Medicine and Cellular Longevity, 2019, 2730896. CrossRef
Jung, K-W., Kwon, S., Jung, J-H., and Bahn, Y-S., 2022, Essential roles of ribonucleotide reductases under DNA damage and replication stresses in Cryptococcus neoformans, Microbiology Spectrum, 10(4), e0104422. CrossRef
Kesuma, D., Yuniarta, T.A., Putra, G.S., Sumari, S., Sulistyowaty, M.I., and Anwari, F., 2022, In silico, synthesis, structure elucidation and anticancer activity study of 2-(3,4-dichlo¬rophenyl)-4H-benzo[d][1,3]oxazin-4-one, Pakistan Journal of Pharmaceutical Sciences, 35(5), 1391–1398. CrossRef
Khan, S.U., Fatima, K., Aisha, S., and Malik, F., 2024, Unveiling the mechanisms and challenges of cancer drug resistance, Cell Communication and Signaling, 22, 109. CrossRef
Lai, H., Wang, L., Qian, R., Huang, J., Zhou, P., Ye, G., et al., 2024, Interformer: an interaction-aware model for protein-ligand docking and affinity prediction, Nature Communications, 15, 10223. CrossRef
Lipinski, C.A., Lombardo, F., Dominy, B.W., and Feeney, P.J., 1997, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Advanced Drug Delivery Reviews, 46(1-3), 3-26. CrossRef
Liu, B., Zhou, H., Tan, L., Siu, K.T.H., and Guan, X.-Y., 2024, Exploring treatment options in cancer: Tumor treatment strategies, Signal Transduction and Targeted Therapy, 9(1), 175. CrossRef
Marwati, M., Alam, G., Yulianty, R., Sami, F.J., Nur, S., Nursamsiar, and Rifai, Y., 2025, In silico evaluation of the glioma activity of reported compounds from the extract Rhodomyrtus tomentosa (Aiton) Hassk., Jurnal Penelitian Pendidikan IPA, 11(6), 215–226. CrossRef
Nivatya, H.K., Singh, A., Kumar, N., Sonam, Sharma, L., Singh, V., et al., 2025, Assessing molecular docking tools: Understanding drug discovery and design, Future Journal of Pharmaceutical Sciences, 11, 111. CrossRef
Oktaviyanti, N.D., Budiono, R., Fitriani, E.W., and Avanti, C., 2024, Optimization ultrasound-assisted extraction using choline chloride-based natural deep eutectic solvent to increase phenolic compounds and antioxidants from Rhodomyrtus tomentosa leaves, International Journal of Applied Pharmaceutics, 16(5), 83–90. CrossRef
Pagadala, N.S., Syed, K. and Tuszynski, J., 2017, Software for molecular docking: A review, Biophysical Reviews, 9(2), 91–102. CrossRef
Paggi, J.M., Pandit, A., and Dror, R.O., 2024, The art and science of molecular docking, Annual Review of Biochemistry, 93, 389–410. CrossRef
Pesaresi, A., 2023, Mixed and non-competitive enzyme inhibition: underlying mechanisms and mechanistic irrelevance of the formal two-site model, Journal of Enzyme Inhibition and Medicinal Chemistry, 38(1), 2245168. CrossRef
Sarmoko, Suprahman, N.Y., Putri, R.A., Zammi, A., Hakim, A.Z.A., Cahyadi, D.R., and Saputra, M.Y., 2025, In silico analysis of Cucurbitacin IIa and Cucurbitacin IIb as potential modulators of oxidative stress regulatory proteins, Indonesian Journal of Cancer Chemoprevention, 15(3), 224–236. CrossRef
Shahidi, F. and Dissanayaka, C.S., 2023, Phenolic-protein interactions: insight from in-silico analyses a review, Food Production, Processing and Nutrition, 5, 2. CrossRef
Tayeh, M. and Watanapokasin, R., 2020, Antimetastatic potential of rhodomyrtone on human chondrosarcoma SW1353 cells, Evidence-Based Complementary and Alternative Medicine, 2020, 8180261. CrossRef
Thomsen, R. and Christensen, M.H., 2006, MolDock: A New Technique for High-Accuracy Molecular Docking, Journal of Medicinal Chemistry, 49(11), 3315-3321. CrossRef
Vittorio, S., Lunghini, F., Morerio, P., Gadioli, D., Orlandini, S., Silva, P., et al., 2024, Addressing docking pose selection with structure-based deep learning: Recent advances, challenges and opportunities, Computational and Structural Biotechnology Journal, 23, 2141–2151. CrossRef
Vo, T.S. and Ngo, D.H., 2019, The health beneficial properties of Rhodomyrtus tomentosa as potential functional food, Biomolecules, 9(2), 76. CrossRef
Winter, R.C., Amghar, M., Wacker, A.S., Bakos, G., Taş, H., Roscher, M., et al., 2024, Future treatment strategies for cancer patients combining targeted alpha therapy with pillars of cancer treatment: External beam radiation therapy, checkpoint inhibition immunotherapy, cytostatic chemotherapy, and brachytherapy, Pharmaceuricals (Basel, Switzerland), 1(8), 1031. CrossRef
Yuniarta, T.A., Kesuma, D., and Putra, P.P., 2025, Virtual Screening, ADMET Evaluation, and Molecular Docking Approach in the Discovery of Novel Potential Sweetening Agent, MPI (Media Pharmaceutica Indonesiana), 7(2), 124-137. CrossRef
Zhuang, L., Chen, L.-F., Zhang, Y.-B., Liu, Z., Xiao, X.-H., Tang, W., et al., 2017, Watsonianone A from Rhodomyrtus tomentosa fruit attenuates respiratory-syncytial-virus-induced inflammation in vitro, Journal of Agricultural and Food Chemistry, 65(17), 3481–3489. CrossRef
DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev16iss2pp107-122
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