Journal of Multidisciplinary Applied Natural Science
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https://doi.org/10.47352/jmans.2774-3047.471
Muhammad Badrul Huda
Nurlelasari Nurlelasari
Faris Hermawan
Wahyu Safriansyah
Unang Supratman
Yudha Prawira Budiman
Dysobinin is a naturally occurring limonoid and a type of triterpenoid, which shows certain efficacy, although its prospects in the field of pharmacology are still limited. Therefore, this study aimed to improve the pharmacological properties of dysobinin through structural rearrangement. A 56% yield was obtained using Selectfluor to convert dysobinin into a novel molecule, specifically 22α-carboxyacid-dysobinin (5). Compared to the other compounds, 22α-carboxyacid-dysobinin (5) exhibited significantly higher cytotoxicity against human epithelial tumor (HeLa) and B16-F10 cancer cells. However, this compound 5 exhibited the lowest cytotoxicity against MCF-7 cancer cells. Subsequently, a docking study showed that compound 5 had binding energies of -9.61, -7.81, and -6.08 kcal/mol for EGFR, Bcl-2, and Tyrosinase, respectively. In the prediction of pharmacokinetic parameters, compound 5 fulfilled the minimum standard parameters for the ADMET properties. Therefore, compound 5 may be considered a promising lead compound for anticancer development, warranting further optimization and validation.
[1] R. L. Siegel, K. D. Miller, N. S. Wagle, and A. Jemal. (2023). "Cancer statistics, 2023". CA: A Cancer Journal for Clinicians. 73 (1): 17-48. 10.3322/caac.21763.
DOI: https://doi.org/10.3322/caac.21763[2] F. Bray, M. Laversanne, H. Sung, J. Ferlay, R. L. Siegel, I. Soerjomataram, and A. Jemal. (2024). "Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries". CA: A Cancer Journal for Clinicians. 74 : 229-263. 10.3322/caac.21834.
DOI: https://doi.org/10.3322/caac.21834[3] C. B. Blackadar. (2016). "Historical Review of the Causes of Cancer". World Journal of Clinical Oncology. 7 (1): 54-86. 10.5306/wjco.v7.i1.54.
DOI: https://doi.org/10.5306/wjco.v7.i1.54[4] M. P. Crespo-Ortiz and M. Q. Wei. (2012). "Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug". Journal of Biomedicine and Biotechnology. 2012 : 247597. 10.1155/2012/247597.
DOI: https://doi.org/10.1155/2012/247597[5] G. Danaei, S. Vander Hoorn, A. D. Lopez, C. J. L. Murray, and M. Ezzati. (2005). "Causes of Cancer in the World: Comparative Risk Assessment of Nine Behavioural and Environmental Risk Factors". The Lancet. 366 : 1784-1793. 10.1016/S0140-6736(05)67725-2.
DOI: https://doi.org/10.1016/S0140-6736(05)67725-2[6] Q. Li, Z. Shi, F. Zhang, W. Zeng, D. Zhu, and L. Mei. (2022). "Symphony of Nanomaterials and Immunotherapy Based on the Cancer-Immunity Cycle". Acta Pharmaceutica Sinica B. 12 : 107-134. 10.1016/j.apsb.2021.05.031.
DOI: https://doi.org/10.1016/j.apsb.2021.05.031[7] U. Supratman, Supriatno, W. Naibaho, M. Fajar, Nurlelasari, D. G. Katja, D. Harneti, R. Maharani, A. T. Hidayat, R. Lesmana, M. A. Nafiah, and Y. Shiono. (2020). "New Cytotoxic Limonoids from the Stem Bark of Chisocheton pentandrus (Blanco) Merr". Phytochemistry Letters. 35 : 63-67. 10.1016/j.phytol.2019.11.002.
DOI: https://doi.org/10.1016/j.phytol.2019.11.002[8] Nurlelasari, I. Rahmayanti, S. Salam, A. Safari, D. Harneti, R. Maharani, A. T. Hidayat, M. Tanjung, R. Retnowati, Y. Shiono, and U. Supratman. (2021). "A New Havanensin-Type Limonoid from Chisocheton macrophyllus". Applied Biological Chemistry. 64 (1): 1-6. 10.1186/s13765-021-00606-5.
DOI: https://doi.org/10.1186/s13765-021-00606-5[9] E. Hilmayanti, Nurlelasari, D. G. Katja, A. T. Hidayat, S. Fajriah, A. Darmawan, U. Supratman, M. N. Azmi, and Y. Shiono. (2022). "Azadirone-Type Limonoids from the Fruit of Chisocheton lasiocarpus and Their Cytotoxic Activity Against MCF-7 Breast Cancer Cells". Molekul. 17 (1): 60-67. 10.20884/1.jm.2022.17.1.5593.
DOI: https://doi.org/10.20884/1.jm.2022.17.1.5593[10] S. L. Chong, A. Hematpoor, Hazni, M. S. Azirun, M. Litaudon, U. Supratman, M. Murata, and K. Awang. (2019). "Mosquito Larvicidal Limonoids from the Fruits of Chisocheton erythrocarpus Hiern". Phytochemistry Letters. 30 : 69-73. 10.1016/j.phytol.2018.12.013.
DOI: https://doi.org/10.1016/j.phytol.2018.12.013[11] Nurlelasari, L. W. Azzahra, W. Safriansyah, M. B. Huda, Rustaman, D. Harneti, T. Mayanti, K. Farabi, R. Maharani, and U. Supratman. (2026). "11α-Hydroxydysobinin: A New Limonoid from Chisocheton macrophyllus Seeds (Meliaceae)". Journal of Asian Natural Products Research. 28 : 635-642. 10.1080/10286020.2025.2525332.
DOI: https://doi.org/10.1080/10286020.2025.2525332[12] M. B. Mukesh and K. Rakesh. (2011). "Molecular Docking: A Review". International Journal of Ayurveda and Pharmacy. 2 (6): 1746-1750.
[13] C. Sha and P. C. Lee. (2024). "EGFR-Targeted Therapies: A Literature Review". Journal of Clinical Medicine. 13 : 6391. 10.3390/jcm13216391.
DOI: https://doi.org/10.3390/jcm13216391[14] A. Hawash. (2024). "Targeting EGFR Signaling in Cancer: Mechanisms and Therapeutic Strategies". Cells. 13 (19): 1656. 10.3390/cells13191656.
DOI: https://doi.org/10.3390/cells13191656[15] A. Ayati, S. Moghimi, S. Salarinejad, M. Safavi, B. Pouramiri, and A. Foroumadi. (2020). "A Review on Progression of Epidermal Growth Factor Receptor (EGFR) Inhibitors as an Efficient Approach in Cancer Therapy". Bioorganic Chemistry. 99 : 103811. 10.1016/j.bioorg.2020.103811.
DOI: https://doi.org/10.1016/j.bioorg.2020.103811[16] G. Zhao, W. Wang, L. Zheng, L. Chen, G. Duan, R. Chang, Z. Chen, S. Zhang, M. Dai, and G. Yang. (2023). "Catalase-Peroxidase StKatG Is a Bacterial Manganese Oxidase from Endophytic Salinicola tamaricis". International Journal of Biological Macromolecules. 224 : 281-291. 10.1016/j.ijbiomac.2022.10.123.
DOI: https://doi.org/10.1016/j.ijbiomac.2022.10.123[17] M. Chatatikun, T. Yamauchi, K. Yamasaki, and S. Aiba. (2018). "Anti-Melanogenic Effect of Croton roxburghii and Croton sublyratus Leaves in α-MSH-Stimulated B16F10 Cells". Journal of Traditional Chinese Medical Sciences. 5 : 1-7. 10.1016/j.jtcme.2017.12.002.
DOI: https://doi.org/10.1016/j.jtcme.2017.12.002[18] Y. H. Cho, J. E. Park, D. S. Lim, and J. S. Lee. (2017). "Tranexamic Acid Inhibits Melanogenesis by Activating the Autophagy System in Cultured Melanoma Cells". Journal of Dermatological Science. 88 (1): 96-102. 10.1016/j.jdermsci.2017.05.019.
DOI: https://doi.org/10.1016/j.jdermsci.2017.05.019[19] R. Jiang, X. H. Xu, and K. Wang. (2017). "Ethyl Acetate Extract from Panax ginseng C.A. Meyer and Its Main Constituents Inhibit α-Melanocyte-Stimulating Hormone-Induced Melanogenesis by Suppressing Oxidative Stress in B16 Mouse Melanoma Cells". Journal of Ethnopharmacology. 208 : 149-156. 10.1016/j.jep.2017.07.004.
DOI: https://doi.org/10.1016/j.jep.2017.07.004[20] T. Pillaiyar, M. Manickam, and S. H. Jung. (2017). "Recent Development of Signaling Pathway Inhibitors of Melanogenesis". Cell Signalling. 40 : 99-115. 10.1016/j.cellsig.2017.09.004.
DOI: https://doi.org/10.1016/j.cellsig.2017.09.004[21] D. W. Robbins and J. F. Hartwig. (2012). "A C-H Borylation Approach to Suzuki-Miyaura Coupling of Typically Unstable 2-Heteroaryl and Polyfluorophenyl Boronates". Organic Letters. 14 (16): 4266-4269. 10.1021/ol301570t.
DOI: https://doi.org/10.1021/ol301570t[22] M. B. Huda, Nurlelasari, W. Safriansyah, M. Fajar, I. I. Widiyowati, U. Supratman, Y. Permana, and Y. P. Budiman. (2024). "One-Pot Two-Step Borylation/Fluorination Reaction of Dysobinin from Chisocheton macrophyllus and Its Cytotoxicity Against Cancer Cells". Communications in Science and Technology. 9 : 366-371. 10.21924/cst.9.2.2024.1514.
DOI: https://doi.org/10.21924/cst.9.2.2024.1514[23] E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenblatt, E. C. Meng, and T. E. Ferrin. (2004). "UCSF Chimera: A Visualization System for Exploratory Research and Analysis". Journal of Computational Chemistry. 25 (13): 1605-1612. 10.1002/jcc.20084.
DOI: https://doi.org/10.1002/jcc.20084[24] M. D. Hanwell, D. E. Curtis, D. C. Lonie, T. Vandermeersch, E. Zurek, and G. R. Hutchison. (2012). "Avogadro: An Advanced Semantic Chemical Editor, Visualization, and Analysis Platform". Journal of Cheminformatics. 4 : 17. 10.1186/1758-2946-4-17.
DOI: https://doi.org/10.1186/1758-2946-4-17[25] F. Neese. (2012). "The ORCA Program System". Wiley Interdisciplinary Reviews: Computational Molecular Science. 2 (1): 73-78. 10.1002/wcms.81.
DOI: https://doi.org/10.1002/wcms.81[26] D. E. V. Pires, T. L. Blundell, and D. B. Ascher. (2015). "pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures". Journal of Medicinal Chemistry. 58 (9): 4066-4072. 10.1021/acs.jmedchem.5b00104.
DOI: https://doi.org/10.1021/acs.jmedchem.5b00104[27] Nurlelasari, M. B. Huda, W. Safriansyah, U. Supratman, Y. P. Budiman, D. H. P. Huspa, R. Maharani, T. Mayanti, K. Farabi, and S. Fajriah. (2024). "A Novel Limonoid from the Seeds of Chisocheton macrophyllus". Records of Natural Products. 18 (3): 347-351. 10.25135/rnp.451.2311.2960.
[28] G. Isabelle, I. Dondasse, C. Nicolas, L. Mimoun, V. Sukach, and H. Meudal. (2022). "Iridium-Catalyzed β-C(sp2)-H Borylation of Enamides: Access to 3,3-Dihalogeno-2-Methoxypiperidines". European Journal of Organic Chemistry. 2022 (2). 10.1002/ejoc.202101302.
DOI: https://doi.org/10.1002/ejoc.202101302[29] S. J. Blank and C. E. Stephens. (2006). "Oxidative Ring Opening of 2,5-Diarylfurans by Selectfluor". Tetrahedron Letters. 47 (38): 6849-6850. 10.1016/j.tetlet.2006.07.071.
DOI: https://doi.org/10.1016/j.tetlet.2006.07.071[30] H. Wang, S. Ren, J. Zhang, W. Zhang, and Y. Liu. (2015). "Selectfluor-Mediated Simultaneous Cleavage of C-O and C-C Bonds in α,β-Epoxy Ketones Under Transition-Metal-Free Conditions: A Route to 1,2-Diketones". Journal of Organic Chemistry. 80 (13): 6856-6863. 10.1021/acs.joc.5b00857.
DOI: https://doi.org/10.1021/acs.joc.5b00857[31] Y. L. Zhang, C. C. Chiang, Y. T. Lee, Z. H. Wen, Y. C. Wu, Y. J. Wu, T. L. Hwang, T. Y. Wu, C. Y. Chang, and P. J. Sung. (2020). "Briarenols Q-T: Briaranes from A Cultured Octocoral Briareum stechei (Kukenthal, 1908)". Marine Drugs. 18 (8). 10.3390/md18080383.
DOI: https://doi.org/10.3390/md18080383[32] W. Safriansyah, F. F. Abdullah, E. Juliansyah, K. Farabi, Harizon, H. Kuncoro, Nurlelasari, R. Maharani, M. N. A. Mohamad Taib, U. Supratman, and D. Harneti. (2023). "Sesquiterpenoids from the Stem Bark of Aglaia pachyphylla Miq (Meliaceae) and Cytotoxic Activity Against MCF-7 Cancer Cell Line". Jurnal Kimia Valensi. 9 (2): 300-305. 10.15408/jkv.v9i2.32782.
DOI: https://doi.org/10.15408/jkv.v9i2.32782[33] S. Supriatno, Nurlelasari, T. Herlina, D. Harneti, R. Maharani, A. T. Hidayat, T. Mayanti, U. Supratman, M. N. Azmi, and Y. Shiono. (2018). "A New Limonoid from the Stem Bark of Chisocheton pentandrus (Meliaceae)". Natural Product Research. 32 : 1-7. 10.1080/14786419.2018.1428600.
DOI: https://doi.org/10.1080/14786419.2018.1428600[34] Q. Wang, B. Kou, J. Wang, H. Song, J. Gao, Y. Sun, L. Wang, and X. Jin. (2025). "Limonoids and Semisynthetic Derivatives as Anticancer Agents: Recent Research Progress and Future Perspectives". Bioorganic Chemistry. 161 : 108520. 10.1016/j.bioorg.2025.108520.
DOI: https://doi.org/10.1016/j.bioorg.2025.108520[35] X. Z. Wang, H. H. Yang, W. Li, B. J. Han, and Y. J. Liu. (2016). "Studies on Apoptosis in HeLa Cells via the ROS-Mediated Mitochondrial Pathway Induced by New Dibenzoxanthenes". New Journal of Chemistry. 40 (6): 5255-5267. 10.1039/C6NJ00250A.
DOI: https://doi.org/10.1039/C6NJ00250A[36] M. Jopp, J. Becker, S. Becker, A. Miska, V. Gandin, C. Marzano, and S. Schindler. (2017). "Anticancer Activity of a Series of Copper(II) Complexes with Tripodal Ligands". European Journal of Medicinal Chemistry. 132 : 274-281. 10.1016/j.ejmech.2017.03.019.
DOI: https://doi.org/10.1016/j.ejmech.2017.03.019[37] A. C. Martínez-Torres, A. Reyes-Ruiz, K. M. Calvillo-Rodriguez, K. M. Alvarez-Valadez, A. C. Uscanga-Palomeque, R. S. Tamez-Guerra, and C. Rodríguez-Padilla. (2020). "IMMUNEPOTENT CRP Induces DAMPs Release and ROS-Dependent Autophagosome Formation in HeLa and MCF-7 Cells". BMC Cancer. 20 : 647. 10.1186/s12885-020-07124-5.
DOI: https://doi.org/10.1186/s12885-020-07124-5[38] J. Eberhardt, D. Santos-Martins, A. F. Tillack, and S. Forli. (2021). "AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings". Journal of Chemical Information and Modeling. 61 (8): 3891-3898. 10.1021/acs.jcim.1c00203.
DOI: https://doi.org/10.1021/acs.jcim.1c00203[39] Y. S. Kwon, K. S. Nam, and S. Kim. (2021). "Tamoxifen Overcomes Trastuzumab Resistance of SK-BR-3 Tumourspheres by Targeting Crosstalk Between Cytoplasmic Estrogen Receptor α and the EGFR/HER2 Signaling Pathway". Biochemical Pharmacology. 190 : 114635. 10.1016/j.bcp.2021.114635.
DOI: https://doi.org/10.1016/j.bcp.2021.114635[40] P. Zhou, J. Hu, X. Wang, J. Wang, Y. Zhang, and C. Wang. (2018). "Epidermal Growth Factor Receptor Expression Affects Proliferation and Apoptosis in Non-Small Cell Lung Cancer Cells via the Extracellular Signal-Regulated Kinase/MicroRNA-200a Signaling Pathway". Oncology Letters. 15 : 5201-5207. 10.3892/ol.2018.7961.
DOI: https://doi.org/10.3892/ol.2018.7961[41] C. Pan, X. Li, Y. Zhang, Z. Zhang, Y. Li, B. Chen, G. Li, L. Zhang, C. Deng, H. A. Akber, Z. Du, and Z. Yang. (2023). "The Mechanisms of Melanogenesis Inhibition by Glabridin: Molecular Docking, PKA/MITF and MAPK/MITF Pathways". Food Science and Human Wellness. 12 (1): 212-222. 10.1016/j.fshw.2022.07.011.
DOI: https://doi.org/10.1016/j.fshw.2022.07.011[42] T. K. Karami, S. Hailu, S. Feng, R. Graham, and H. J. Gukasyan. (2022). "Eyes on Lipinski's Rule of Five: A New Rule of Thumb for Physicochemical Design Space of Ophthalmic Drugs". Journal of Ocular Pharmacology and Therapeutics. 38 (1): 1-9. 10.1089/jop.2021.0069.
DOI: https://doi.org/10.1089/jop.2021.0069[43] Y. Wang, M. Yu, A. T. Amrouche, F. Jie, S. Ji, and B. Lu. (2023). "Human Intestinal Caco-2 Cell Model to Evaluate the Absorption of Bioactive Compounds and Their Effects on Transport Mechanisms". Food Science and Human Wellness. 12 (5): 1701-1707. 10.1016/j.fshw.2023.02.032.
DOI: https://doi.org/10.1016/j.fshw.2023.02.032[44] E. Radchenko, A. Dyabina, V. Palyulin, and N. Zefirov. (2016). "Prediction of Human Intestinal Absorption of Drug Compounds". Russian Chemical Bulletin. 65 : 576-580. 10.1007/s11172-016-1340-0.
DOI: https://doi.org/10.1007/s11172-016-1340-0[45] N. Flores-Holguin, J. Frau, and D. Glossman-Mitnik. (2021). "Computational Pharmacokinetics Report, ADMET Study, and Conceptual DFT-Based Estimation of the Chemical Reactivity Properties of Marine Cyclopeptides". ChemistryOpen. 10 (11): 1142-1149. 10.1002/open.202100178.
DOI: https://doi.org/10.1002/open.202100178