Molecular Docking Analysis of Flavonoids from Syzygium cumini (L.) Skeels: Proapoptotic Potential as an Anticancer Mechanism
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Submitted
15 May 2025
Published
30 August 2025
Keywords:
-
NSCLC, Syzigium cumini (L.) Skeels, In silico
Abstract
Non-small cell lung cancer (NSCLC) presents a significant global health challenge, with its prevalence and mortality rates rising steadily. In Indonesia, Syzygium cumini (L.) Skeels, known for its flavonoid richness, has a long history in traditional medicine. However, its specific mechanisms of action against cancer, particularly in inducing apoptosis in NSCLC, have not been fully elucidated. This study utilized an in silico approach to evaluate the pro-apoptotic potential of S. cumini flavonoids against NSCLC by targeting key proteins: Bcl-2, Bax, and Caspase-3. We retrieved flavonoid structures from PubChem and protein data from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB). The drug-likeness of these compounds was assessed using Swiss ADME, adhering to Lipinski's rule of five, while their anti-NSCLC probability was predicted using PASS Online. Molecular docking and screening were performed with PyRx, and the results were visualized using Discovery Studio. Our findings identified epigallocatechin 3-O-gallate and ellagic acid as the most promising anti-NSCLC candidates. Ellagic acid demonstrated the strongest binding affinity to Caspase-3, suggesting a potent pro-apoptotic effect. Epigallocatechin 3-O-gallate, on the other hand, exhibited the lowest binding energy across multiple target proteins, particularly Bcl-2 and Bax, indicating its broad pro-apoptotic potential. These results collectively suggest that flavonoids from S. cumini may hold significant promise as a source of novel anti-NSCLC agents, warranting further in vitro and in vivo investigations.
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References
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17. Christina YI, Nafisah W, Atho’illah MF, Rifa’i M, Widodo N, et al. Anti-breast cancer potential activity of Phaleria macrocarpa (Scheff.) Boerl. leaf extract through in silico studies. J Pharm Pharmacogn Res. 2021;9(6):824-45. DOI: 10.56499/jppres21.1092_9.6.824
18. Li Y, Wang Y, Yu X, Yu T, Zheng X, Chu Q. Radix tetrastigma inhibits the non-small cell lung cancer via Bax/Bcl-2/Caspase-9/Caspase-3 pathway. Nutr Cancer. 2021;74(1):320-32. DOI: 10.1080/01635581.2021.1881569; PMID: 33586527
19. Gibbert L, Sereno AB, de Andrade MTP, Miguel MD, Montrucchio DP, de Messias-Reason IJ, et al. Nutritional caomposition, antioxidant activity and anticancer potential of Syzygium cumini (L.) and Syzygium malaccense (L.) fruits. Res Soc Dev. 2021;10(4):e5210413743. DOI: 10.33448/rsd-v10i4.13743
20. Putri EBP, Rozaki RD. A comparative assessment of chemical characteristics of goat’s milk yoghurt after the addition of Syzygium cumini L. Bali Med J. 2022; 11(2): 692–6. DOI: 10.15562/bmj.v11i2.3138
21. Qamar M, Akhtar S, Ismail T, Wahid M, Abbas MW, Mubarak MS, et al. Phytochemical profile, biological properties, and food applications of the medicinal plant Syzygium cumini. Foods. 2022;11(3):378. DOI: 10.3390/foods11030378; PMCID: PMC8834268; PMID; 35159528
22. Baliga MS, Fernandes S, Thilakchand KR, D’souza P, Rao S. Scientific validation of the antidiabetic effects of Syzygium jambolanum DC (black plum), a traditional medicinal plant of India. J Altern Complement Med. 2013;191(3):191-7. DOI: 10.1089/acm.2011.0752; PMID: 23030429
23. Tavares IMdC, Lago-Vanzela ES, Rebello LPG, Ramos AM, Gomez-Alonso S, García-Romero E, et al. Comprehensive study of the phenolic composition of the edible parts of jambolan fruit (Syzygium cumini (L.) Skeels). Food Res Int. 2016;82:1-13. DOI: 10.1016/j.foodres.2016.01.014
24. Ghosh P, Radha NRC, Mishra S, Patel AS, Kar A. Physicochemical and nutritional characterization of jamun (Syzygium cumini). Curr Res Nutr Food Sci J. 2017;5(1):25-35. DOI: 10.12944/CRNFSJ.5.1.04
25. Seraglio SKT, Schuls M, Nehring P, Betta FD, Valese AC, Daguer H, et al. Nutritional and bioactive potential of Myrtaceae fruits during ripening. Food Chem. 2018;239(15):649-56. DOI: 10.1016/j.foodchem.2017.06.118; PMID: 28873617
26. Yadav SS, Meshram GA, Shinde D, Patil RC, Manohar SM, & Upadhye MV. Antibacterial and anticancer activity of bioactive fraction of Syzygium cumini L. seeds. Hayati J Biosci. 2011;18(3):118-22. DOI: 10.4308/hjb.18.3.118
27. Tripathy G, Pradhan D, Pradhan S, Dasmohaptra T. Evaluation of plant extracts against lung cancer using H460 cell line. Asian J Pharm Clin Res. 2016;9(2):227-9.
28. Pinto GP, Hendrikse NM, Stourac J, Damborsky J, Bednar D. Virtual screening of potential anticancer drugs based on microbial products. Semin Cancer Biol. 2022;86(2):1207-17. DOI: 10.1016/j.semcancer.2021.07.012; PMID: 34298109
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31. Hartati FK, Djauhari AB, Kharisma VD. Evaluation of pharmacokinetic properties, toxicity, and bioactive cytotoxic activity of black rice (Oryza sativa L.) as candidates for diabetes mellitus drugs by in silico. Biointerface Res Appl Chem. 2021;11(4):12301-11. DOI: 10.33263/BRIAC114.1230112311
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Authors
1.
Aini NS, Ansori ANM, Widyananda MH, Kharisma VD, Murtadlo AAA, Herdiansyah MA, Rebezov M, Burkov P, Gudz P, Derkho M, Bezhinar T, Maksimiuk N, Sazali M, Purnobasuki H, Rollando R, Khairullah AR, Sucipto TH. Molecular Docking Analysis of Flavonoids from Syzygium cumini (L.) Skeels: Proapoptotic Potential as an Anticancer Mechanism. Borneo J Pharm [Internet]. 2025Aug.30 [cited 2025Dec.5];8(3):252-6. Available from: https://journal.umpr.ac.id/index.php/bjop/article/view/9843
Copyright (c) 2025 Nur Sofiatul Aini, Arif Nur Muhammad Ansori, Muhammad Hermawan Widyananda, Viol Dhea Kharisma, Ahmad Affan Ali Murtadlo, Mochammad Aqilah Herdiansyah, Maksim Rebezov, Pavel Burkov, Petr Gudz, Marina Derkho, Tatyana Bezhinar, Nikolai Maksimiuk, Munawir Sazali, Hery Purnobasuki, Rollando Rollando, Aswin Rafif Khairullah, Teguh Hari Sucipto
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