Syzydyerin A, a new unusual C-methylated chalcone isolated from the leaves of Syzygium dyerianum (King) Chantar. & J.Parn
-
Faezatul Alwani Mohd Rahim
, Wan Mohd Nuzul Hakimi Wan Salleh, Nurunajah Ab Ghani
, Abubakar Siddiq Salihu , Mohd Hafiz Arzmi und David Barker
Abstract
A new unusual C-methylated chalcone was successfully isolated from the leaves of Syzygium dyerianum (King) Chantaran. & J.Parn, identified as syzydyerin A (1), together with β-sitosterol, friedelin and lupeol. The characterisation and structural elucidation of the isolated compounds were established by extensive spectroscopic data analysis and comparison with literature data. Compound 1 exhibited inhibitory activity against acetylcholinesterase (AChE) and lipoxygenase (LOX) with IC50 values of 50.4 ± 0.2 µm and 30.7 ± 0.25 µm, respectively, compared to the reference inhibitors galantamine (IC50 = 40.7 ± 0.12 µm) for AChE and quercetin (IC50 = 3.5 ± 0.13 µm) 5-LOX. Molecular docking analysis revealed that compound 1 exhibits strong binding affinities toward AChE (−11.0 kcal/mol) and 5-LOX (−9.1 kcal/mol), comparable to standard inhibitors, with key π–π stacking and hydrogen bonding interactions stabilizing its binding at both active sites, highlighting its promising dual inhibitory potential. The study underscores the value of S. dyerianum as a source of bioactive compounds with potential applications in treating neuroinflammatory diseases.
Funding source: Universiti Pendidikan Sultan Idris
Award Identifier / Grant number: 2025-0012-103-01
Acknowledgments
The authors would like to express their sincere gratitude to Department of Chemistry, Faculty of Science and Mathematics, UPSI for providing the facilities and resources throughout this study.
-
Research ethics: Not applicable.
-
Informed consent: Not applicable.
-
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
-
Use of Large Language Models, AI and Machine Learning Tools: None declared.
-
Conflict of interest: The authors declare no conflicts of interest regarding this article.
-
Research funding: This research was supported by the Geran Penyelidikan Universiti (Kecemerlangan@UPSI) under grant number 2025-0012-103-01, funded by Universiti Pendidikan Sultan Idris.
-
Data availability: All data supporting the findings of this study are included within the article and its supplementary materials.
References
1. Rahim, FAM, Salleh, WMNHW, Salihu, AS, Arrmi, MH. Chemical composition of the essential oil of Syzygium wrayi. Chem Nat Compd 2024;60:1155–7. https://doi.org/10.1007/s10600-024-04544-8.Suche in Google Scholar
2. Rahim, FAM, Salleh, WMNHW, Arzmi, MH, Salihu, AS. Chemical composition and antibiofilm of the essential oil of Syzygium cinereum. Chem Nat Compd 2024;60:774–5. https://doi.org/10.1007/s10600-024-04440-1.Suche in Google Scholar
3. Rahim, FAM, Salleh, WMNHW, Ghani, NA, Salihu, AS. Analysis of essential oil from Syzygium cerinum. Chem Nat Compd 2024;60:345–6. https://doi.org/10.1007/s10600-024-04320-8.Suche in Google Scholar
4. Aung, EE, Kristanti, AN, Aminah, NS, Takaya, Y, Ramadhan, R. Plant description, phytochemical constituents and bioactivities of syzygium genus: a review. Open Chem 2020;18:1256–81. https://doi.org/10.1515/chem-2020-0175.Suche in Google Scholar
5. Hussin, KH, Cutler, DF, Moore, DM. Leaf anatomical studies of Eugenia L. (myrtaceae) species from the Malay peninsula. Bot J Linn Soc 1992;110:137–56. https://doi.org/10.1111/j.1095-8339.1992.tb00287.x.Suche in Google Scholar
6. Rahim, FAM, Salleh, WMNHW, Arzmi, MH, Salihu, AS. Chemical composition, antifungal, antibiofilm, and molecular docking studies of Syzygium dyerianum essential oil. Z Naturforsch, C: J Biosci 2024;79:179–86. https://doi.org/10.1515/znc-2023-0133.Suche in Google Scholar PubMed
7. Salleh, WMNHW, Ahmad, F, Khong, HY, Zulkifli, RM, Sarker, SD. Madangones A and B: two new neolignans from the stem bark of Beilschmiedia Madang and their bioactivities. Phytochem Lett 2016;15:168–73. https://doi.org/10.1016/j.phytol.2016.01.004.Suche in Google Scholar
8. Salleh, WMNHW, Sazali, NSAN, Ahmad, F, Taher, M. Biflavonoids from the leaves and stem bark of Garcinia griffithii and their biological activities. Marmara Pharm J 2017;21:889–97. https://doi.org/10.12991/mpj.2017.27.Suche in Google Scholar
9. Salleh, WMNHW, Ahmad, F, Khong, HY, Zulkifli, RM, Chen, JJ, Nahar, L, et al.. Beilschglabrines A and B: two new bioactive phenanthrene alkaloids from the stem bark of Beilschmiedia glabra. Phytochem Lett 2016;16:192–6. https://doi.org/10.1016/j.phytol.2016.04.013.Suche in Google Scholar
10. Salleh, WMNHW, Nafiah, MA, Yen, KH, Kassim, H, Tawang, A. Chemical constituents and acetylcholinesterase inhibitory activity of Piper abbreviatum opiz. Bull Chem Soc Ethiop 2020;34:625–32. https://doi.org/10.4314/bcse.v34i3.17.Suche in Google Scholar
11. Systèmes, D. BIOVIA materials studio [Internet]. Paris, France: Dassault Systèmes; 2025. Available from: https://www.3ds.com/products/biovia/materials-studio.Suche in Google Scholar
12. Frisch, MJ, Trucks, GW, Schlegel, HB, Scuseria, GE, Robb, MA, Cheeseman, JR, et al.. Gaussian 03. Revision C.02 [Internet]. Berlin, Germany: ScienceOpen, Inc.; 2003. Available from: https://www.scienceopen.com/document?vid=c6dcfe99-1f71-437a-b4ed-ab662a8383f3.Suche in Google Scholar
13. Salihu, AS, Salleh, WMNHW, Ghani, NA, Arzmi, MH, Sungthong, B, Kapavarapu, R. Unraveling bioactive constituents isolated from Knema hookeriana warb. as potential acetylcholinesterase inhibitors. OBM Neurobiol 2025;9:1–17. https://doi.org/10.21926/obm.neurobiol.2502286.Suche in Google Scholar
14. Choommongkol, V, Punturee, K, Klumphu, P, Rattanaburi, P, Meepowpan, P, Suttiarporn, P. Extraction of anticancer flavonoid, 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC), rich in extract of Syzygium nervosum fruits. Molecules 2022;27:1397. https://doi.org/10.3390/molecules27041397.Suche in Google Scholar PubMed PubMed Central
15. Chailungka, A, Junpirom, T, Pompimon, W, Nuntasaen, N, Meepowpan, P. Two flavonoids first isolated from the seed of Syzygium nervosum and preliminary study of their anticancer and anti-HIV-1 reverse transcriptase activities. Maejo Int J Sci Tech 2017;11:58–67.Suche in Google Scholar
16. Amor, EC, Villasenor, IM, Antemano, R, Perveen, Z, Conception, GP, Choudhary, MI. Cytotoxic c-methylated chalcones from Syzygium samarangense. Pharm Biol 2007;45:777–83. https://doi.org/10.1080/13880200701585956.Suche in Google Scholar
17. Liu, W, Feng, Y, Yu, S, Fan, Z, Li, X, Li, J, et al.. The flavonoid biosynthesis network in plants. Int J Mol Sci 2021;22:12834. https://doi.org/10.3390/ijms222312824.Suche in Google Scholar PubMed PubMed Central
18. Lewis, JA, Jacobo, EP, Palmer, N, Vermerris, W, Sattler, SE, Brozik, JA, et al.. Structural and interaction analysis of the flavonoid pathway proteins: chalcone synthase, chalcone isomerase and chalcone isomerase-like protein. Int J Mol Sci 2024;25:5651. https://doi.org/10.3390/ijms25115651.Suche in Google Scholar PubMed PubMed Central
19. Kaur, R, Aslam, L, Hussain, S, Kapoor, N, Majahan, R. Flavonoid biosynthetic pathway: genetics and biochemistry. Biosci Biotechnol Res Asia 2021;18:271–86. https://doi.org/10.13005/bbra/2914.Suche in Google Scholar
20. Itoh, N, Iwata, C, Toda, H. Molecular cloning and characterization of a flavonoid-O-methyltransferase with broad substrate specificity and regioselectivity from citrus depressa. BMC Plant Biol 2016;16:180. https://doi.org/10.1186/s12870-016-0870-9.Suche in Google Scholar PubMed PubMed Central
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/znc-2025-0179).
© 2025 Walter de Gruyter GmbH, Berlin/Boston