Two N-Phenyl-Carbamic Acid Methyl Esters from Spatholobus littoralis and their Cytotoxic Effect Against Breast Cancer Using In Vitro and In Silico Methods
Article Sidebar
Views | PDF/EPUB Downloads:
96
/ 47
/ 37
Main Article Content
Abstract
Spatholobus littoralis is an herbal plant widely used in traditional medicine in Kalimantan, Indonesia. This study aimed to isolate and characterize phytoconstituents from the wood of Spatholobus littoralis, and evaluate their cytotoxic activity against breast cancer cells in vitro and in silico. The ethanol extract was fractionated by solvent-solvent partitioning using n-hexane, chloroform, and ethyl acetate sequentially. The chloroform fraction was subjected to gravity silica gel column chromatography using various solvent system to isolate the phytoconstituents. The structures of the isolated compounds were determined using a combination of spectroscopic techniques, including ultra-violet (UV), infra-red (IR), 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and liquid chromatography-high resolution mass spectrometry (LC-HRMS). The cytotoxic activity of the isolated compounds was tested against T47D and 4T1 breast cancer cells, and their potential activity against breast cancer receptor (2IOG) was also studied in silico using molecular docking simulations. The chromatographic separation of the chloroform fraction of Spatholobus littoralis wood led to the isolation of two carbamic acid esters characterized as dimethyl (methylene bis(4,1-phenylene)) dicarbamate (1) and asperteramide A (2). Compound 1 was cytotoxic to 4T1 cancer cells with an IC50 of 84.82 µg/mL, while compound 2 was cytotoxic to T47D with an IC50 of 134.71 µg/mL. Compounds 1 and 2 showed high affinity with the 2IOG receptor with binding affinity of -6.8 and -8.1 kcal/mol, respectively. Therefore, S. littoralis wood extract has the potential to be developed as a natural source of anticancer agents against breast cancer.
Downloads
Article Details
Section
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
References
1.Ridder-Numan JWA and Wiriadinata HA. Revision of the Genus Spatholobus (Leguminosae-Papilionoideae). J Taxon Bot. 1985; 10(2):107–270.
2.Liu Y, Xiang Q, Liang Q, Shi J, He J. Genus Spatholobus: a Comprehensive Review on Ethnopharmacology, Phytochemistry, Pharmacology, and Toxicology. Food Funct. 2022; 18(13):7448-7472.
3.Hamzah H, Pratiwi SUT, Jabbar A, Hafifah AS, Al-Fajri BA, Nurhalisah N. Bioactivity Tracing of the Ethanol Extract of Bajakah Tampala (Spatholobus littoralis Hassk.) Typical Plant of Kalimantan Island as Antibiofilm of Staphylococcus aureus. Open Access Maced J Med Sci. 2023; 11:8–14.
4.Nurkhasanah M, Dwi U, Siti N, Mustofa A, Andika A, Sabilla GA. Variability and Pharmacological Potential of Bajakah (Spatholobus sp.) as an Indigenous Medicinal Plant: A Review. Int J Pub Health Sci. 2024; 13(3):1470-1479.
5.Atun S, Aznam N, Arianingrum R, Rasningtyaswati, Sangal A. Cytotoxic Effect of Spatholobus littoralis Extract on Breast Cancer Cells by in Vitro and Prediction of the Mechanism of Activity Against Estrogen Receptors (ER-α and ER-β) by in Silico. J Herbmed Pharmacol. 2025; 14(1):19-28.
6.Iskandar D, Widodo N, Warsito, Masruri, Rollando, Antang YP. Phenolic Content, Antioxidant, Cytotoxic of Fractions of Spatholobus littoralis Hassk from Kalimantan, Indonesia. J Hunan Univ Nat Sci. 2022; 49(3):14-23.
7.Hadanu R, Irwansyah GP, Sartika, Wahyuningrum R. Compound Characterization and Evaluation of Antioxidant Potential of Ethanol Extract Spatholobus littoralis Hassk in Kolaka, Southeast Sulawesi, Indonesia. J Pharm Res Int. 2023; 35(28):59-70.
8.Sianipar RNR, Suryanegara L, Fatriasari W, Arung ET, Kusuma IW, Achmadi SS, Azelee NIW, Hamid ZAA. The Role of Selected Flavonoids from Bajakah Tampala (Spatholobus littoralis Hassk.) Stem on Cosmetic Properties: A Review. Saudi Pharm J. 2023; 31:382-400.
9.Atun S, Aznam N, Suwardi S, Nurjanah S, Az-Zahra R, Garinda CBA, Damara R, Octaviani E, Sangal A. Anti-Inflammatory Activity of Some Characteristic Constituents of Spatholobus littoralis Root Wood Extract: In Vitro and In Silico Studies. Trop J Nat Prod Res. 2025; 9(4):1818–1823.
10.Rahmawati DR, Nurrochmad A, Jenie RI, Meiyanto E. The Synergistic Cytotoxic Effect of Pentagamavunon-1 (PGV-1) and Curcumin Correlates with the Cell Cycle Arrest to Induce Mitotic Catastrophe in 4T1 and T47D Breast Cancer Cells. Indones Biomed J. 2023; 15(5):318-327.
11.Sajjadi SE, Ghanadian M, Haghighi M, Mouhebat L. Cytotoxic Effect of Cousinia verbascifolia Bunge Against OVCAR-3 and HT-29 Cancer Cells. J Herbmed Pharmacol. 2015; 4(1):15-19.
12.Rajagopal K, Kalusalingam A, Bharathidasan AR, Sivaprakash A, Shanmugam K, Sundaramoorth M, Byran G. In Silico Drug Design of Anti-Breast Cancer Agents. Molecules. 2023; 28:4175-4181.
13.Bagaria A, Jaravine V, Huang YJ, Montelione GT, Güntert P. Protein Structure Validation by Generalized Linear Model Root-Mean-Square Deviation Prediction. Protein Sci. 2012; 21(2):229-238.
14.Chang HS, Cheng MJ, Chen IS. Secondary Methabolites from Magnolia kachirachirai. Helv Chim Acta. 2011; 94(4):703-710.
15.Liu M, He Y, Shen L, Al Anbari WA, Li H, Wang J. Asperteramide A, an Unusual N-Phenyl-Carbamic Acid Methylester Trimer Isolated from the Coral-Derived Fungus Aspergillus terreus. Eur J Org Chem. 2019; 18(15):2928-2932.
16.Peng F, Zhu H, Meng CW, Ren YR, Dai O, Xiong L. New Isoflavanes from Spatholobus suberectus and Their Cytotoxicity Against Human Breast Cancer Cell Lines. Molecules. 2019; 24(18):3218-3226.
17.Li W, Liu J, Guan R, Chen J, Yang D, Zhao Z. Chemical Characterization of Procyanidins from Spatholobus suberectus and Their Antioxidative and Anticancer Activities. J Funct Foods. 2015; 12:468-477.
18.Huang X, Fei Q, Yu S, Liu S, Zhang L, Chen X. A Comprehensive Review: Botany, Phytochemistry, Traditional Uses, Pharmacology, and Toxicology of Spatholobus suberectus Vine Stems. J Ethnopharmacol. 2023; 312:116500.
19.Howell A and Howell SJ. Tamoxifen Evolution. Br J Cancer. 2023; 128:421–425.
20.Gokul MD, Chetan CO, Vishnu M. Interaction Between Estrogen Receptors and p53: A Broader Role for Tamoxifen. Endocrinol. 2025; 166(3):1-12.
21.Du X, Li Y, Xi YL, Ai SM, Liang J, Sang P. Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods. Int J Mol Sci. 2016; 17:1-34.
22.Xia Y, Pan X, Shen HB. A Comprehensive Survey on Protein-Ligand Binding Site Prediction. Curr Opin Struct Biol. 2024; 86:1-10.
23.Koteswara RG, Nikhil RV, Nadeem S, Siva RG, Ankit R, Naveen P. Molecular Docking and Bioactivity Studies of Covalent Inhibitors Targeting RDRP of SARS-COV-2. Rasayan J Chem. 2022; 15:2666-2675.
24.Dela Cruz JMD, Dones SAA, Villanuev RC, Labrador AM, Santiago-Bautista MR. Molecular Docking and In Silico Pharmacological Screening of Oleosin from Cocos nucifera Complexed with Tamoxifen in Developing Potential Breast Chemotherapeutic Leads. Asian Pac J Cancer Prev. 2022; 23(7):2421-2430.
25.Agu PC, Afiukwa CA, Orji OU. Molecular Docking as a Tool for the Discovery of Molecular Targets of Nutraceuticals in Diseases Management. Sci Rep. 2023; 13:13398.