Anticancer Activity Study of Modified Artocarpin Compound from Pudau Plant (Artocarpus kemando Miq.)

Tati Suhartati, Khalimatus Sa’diah, Yandri Yandri, Sutopo Hadi


This research is a continuation of the successful isolation of artocarpin from the root of Artocarpus kemando Miq reported in our previous study. In the previous study, the artocarpin was characterized with UV-Vis and FTIR techniques. In this follow-up investigation, the artocarpin was subjected to a transesterification reaction using acetic anhydride and pyridine as catalysts, and the product of the reaction was specified as compound 1. The compound 1 was further characterized with different techniques to gain more complete data and then tested for anticancer activity test against P-388 murine leukemia cells. Characterizations of the compound 1 using 1H-NMR and 13C-NMR techniques suggest that the modification reaction resulted in the conversion of the -OH groups at C2' and 4' at the artocarpin molecule to -OOCH3, and based on the MS analysis, the compound was proposed to have the molecular formula of C30H32O8. Another important feature of compound 1 that should be noted is the significant improvement in stability compared to the unmodified artocarpin. Anticancer activity tests against P-388 murine leukemia cells revealed that compound 1 has an IC50of 2.35 µg/mL, confirming that the compound is categorized as an active anticancer agent and suggesting that the compound has promising potential that deserves further investigations.


Doi: 10.28991/ESJ-2023-07-03-05

Full Text: PDF


Acetic Anhydride; Artocarpin; Leukemia P-388 Cells; Modification.


Calixto, J. B. (2019). The role of natural products in modern drug discovery. Anais Da Academia Brasileira de Ciencias, 91, 20190105. doi:10.1590/0001-3765201920190105.

Al-Rajhi, A. M. H., Qanash, H., Almuhayawi, M. S., Al Jaouni, S. K., Bakri, M. M., Ganash, M., Salama, H. M., Selim, S., & Abdelghany, T. M. (2022). Molecular Interaction Studies and Phytochemical Characterization of Mentha pulegium L. Constituents with Multiple Biological Utilities as Antioxidant, Antimicrobial, Anticancer and Anti-Hemolytic Agents. Molecules, 27(15), 4824. doi:10.3390/molecules27154824.

Kongkham, B., Prabakaran, D., & Puttaswamy, H. (2020). Opportunities and challenges in managing antibiotic resistance in bacteria using plant secondary metabolites. Fitoterapia, 147, 104762. doi:10.1016/j.fitote.2020.104762.

Lamponi, S. (2021). Bioactive natural compounds with antiplatelet and anticoagulant activity and their potential role in the treatment of thrombotic disorders. Life, 11(10), 1095. doi:10.3390/life11101095.

Sylla, N., Bouyahya, A., Taha, D., Dakka, N., & Elhajji, H. (2021). Study of the antioxidant and antidiabetic activity in vitro of free and encapsulated phenolic compounds of olive pomace. Biocatalysis and Agricultural Biotechnology, 36, 102126. doi:10.1016/j.bcab.2021.102126.

Xue, H., Jiang, Y., Zhao, H., Köllner, T. G., Chen, S., Chen, F., & Chen, F. (2019). Characterization of composition and antifungal properties of leaf secondary metabolites from thirteen cultivars of chrysanthemum morifolium ramat. Molecules, 24(23), 4202. doi:10.3390/molecules24234202.

Querequincia, J. M. B., Osi, M. O., & Sy, S. C. (2021). Phytochemical analysis and assessment of the free radical scavenging activities of the extracts of Artocarpus ovatus Blanco (moraceae) leaves. International Journal of Scientific & Technology Research, 10(4), 133–135.

Nasution, R., Muhabbah, N., Helwati, H., Bahi, M., Marianne, M., & Amna, U. (2020). Isolation of lupeol acetate from fruit peels of Artocarpus camansi. Journal of Advanced Pharmaceutical Technology and Research, 11(3), 148–156. doi:10.4103/japtr.JAPTR_6_20.

Li, G., Ding, K., Qiao, Y., Zhang, L., Zheng, L., Pan, T., & Zhang, L. (2020). Flavonoids regulate inflammation and oxidative stress in cancer. Molecules, 25(23), 5628. doi:10.3390/molecules25235628.

Namdaung, U., Athipornchai, A., Khammee, T., Kuno, M., & Suksamrarn, S. (2018). 2-Arylbenzofurans from Artocarpus lakoocha and methyl ether analogs with potent cholinesterase inhibitory activity. European Journal of Medicinal Chemistry, 143, 1301–1311. doi:10.1016/j.ejmech.2017.10.019.

Hakim, A., Jufri, A. W., Jamaluddin, Supriadi, & Mutmainnah, P. A. (2020). Understanding the Uniqueness of Artocarpus Flavonoids: Isolation and Structure Elucidation of Cycloartocarpin from the Roots of Artocarpus Altilis. Journal of Chemical Education, 97(11), 4133–4136. doi:10.1021/acs.jchemed.0c00199.

Suhartati, T., Fatimah, N., Yandri, Y., Kurniawan, R., Bahri, S., & Hadi, S. (2021). The anticancer, antimalarial, and antibacterial activities of moracalkon a isolated from Artocarpus kemando Miq. Journal of Advanced Pharmacy Education and Research, 11(4), 105–110. doi:10.51847/9NHxpCqzUD.

Ee, G. C. L., Teo, S. H., Rahmani, M., Lim, C. K., Lim, Y. M., & Go, R. (2011). Artomandin, a new xanthone from Artocarpus kemando (Moraceae). Natural Product Research, 25(10), 995–1003. doi:10.1080/14786419.2010.534471.

Ee, G. C. L., Teo, S. H., Rahmani, M., Lim, C. K., Lim, Y. M., & Go, R. (2011). Artomandin, a new xanthone from Artocarpus kemando (Moraceae). Natural product research, 25(10), 995-1003. doi:10.1080/14786419.2010.534471.

Siegel, R. L., Miller, K. D., Fuchs, H. E., & Jemal, A. (2022). Cancer statistics, 2022. CA: A Cancer Journal for Clinicians, 72(1), 7–33. doi:10.3322/caac.21708.

International Agency for Research on Cancer. (2020). Indonesia - Global Cancer Observatory. International Agency for Research on Cancer, World Health Organization (WHO), Geneva, Switzerland. Available online: populations/360-indonesia-fact-sheets.pdf (accessed on January 2023).

Abedinpour, N., Ghanbariasad, A., Taghinezhad, A., & Osanloo, M. (2021). Preparation of Nanoemulsions of Mentha piperita Essential Oil and Investigation of Their Cytotoxic Effect on Human Breast Cancer Lines. BioNanoScience, 11(2), 428–436. doi:10.1007/s12668-021-00827-4.

Forni, C., Rossi, M., Borromeo, I., Feriotto, G., Platamone, G., Tabolacci, C., Mischiati, C., & Beninati, S. (2021). Flavonoids: A myth or a reality for cancer therapy? Molecules, 26(12), 3583. doi:10.3390/molecules26123583.

Musthapa, I., Hakim, E. H., Syah, Y. M., & Juliawaty, L. D. (2016). Cytotoxic activities of prenylated flavonoids from Artocarpus heterophyllus. Journal of Engineering and Applied Sciences, 11(16), 9754-9758.

Suhartati, T., Achmad, S. A., Aimi, N., Hakim, E. H., Kitajima, M., Takayama, H., & Takeya, K. (2001). Artoindonesianin L, a new prenylated flavone with cytotoxic activity from Artocarpus rotunda. Fitoterapia, 72(8), 912–918. doi:10.1016/S0367-326X(01)00343-4.

Suhartati, T. (2001). Phenol Compounds of Several Indonesian Cempedak Plant Species. Ph.D. Thesis, Bandung Institute of Technology, Bandung, Indonesia.

Lin, Q. H., Yuan, J. B., Ma, Z. L., Liang, J., Zhai, X. X., Khan, I. A., Ding, Y. Q., & Ren, G. (2016). Isoprenylated Flavonoids from Roots of Artocarpus styracifolius. Natural Product Communications, 11(12), 1934578X1601101. doi:10.1177/1934578x1601101217.

Patil, A. D., Freyer, A. J., Killmer, L., Offen, P., Taylor, P. B., Votta, B. J., & Johnson, R. K. (2002). A new dimeric dihydrochalcone and a new prenylated flavone from the bud covers of Artocarpus altilis: Potent inhibitors of cathepsin K. Journal of Natural Products, 65(4), 624–627. doi:10.1021/np0105634.

Hashim, N. M., Rahmani, M., Shamaun, S. S., Ee, G. C. L., Sukari, M. A., Manaf Ali, A., & Go, R. (2011). Dipeptide and xanthones from Artocarpus kemando Miq. Journal of Medicinal Plants Research, 5(17), 4224–4230.

Sa’diah, K., Yuwono, S. D., Qudus, H. I., Yandri, & Suhartati, T. (2020). Isolation, Characterization, Modification of Artocarpin Compound from Pudau Plant (Artocarpus kemando Miq.) and Bioactivity Antibacterial Assay of Artocarpin Compound and Their Modification Result. IOP Conference Series: Earth and Environmental Science, 537(1), 012047. doi:10.1088/1755-1315/537/1/012047.

Seo, E. K., Lee, D., Young, G. S., Chai, H. B., Navarro, H. A., Kardono, L. B. S., Rahman, I., Cordell, G. A., Farnsworth, N. R., Pezzuto, J. M., Kinghorn, A. D., Wani, M. C., & Wall, M. E. (2003). Bioactive prenylated flavonoids from the stem bark of Artocarpus kemando. Archives of Pharmacal Research, 26(2), 124–127. doi:10.1007/bf02976656.

Suhartati, T., Wulandari, Z., Wulandari, M., Yandri, & Hadi, S. (2021). Identification and antibacterial activity of flavonoid compounds from wood branches of the pudau plant (Artocarpus kemando Miq.). Journal of Physics: Conference Series, 1751(1), 12095. doi:10.1088/1742-6596/1751/1/012095.

Jalal, T. K., Ahmed, I. A., Mikail, M., Momand, L., Draman, S., Isa, M. L. M., Abdull Rasad, M. S. B., Nor Omar, M., Ibrahim, M., & Abdul Wahab, R. (2015). Evaluation of Antioxidant, Total Phenol and Flavonoid Content and Antimicrobial Activities of Artocarpus altilis (Breadfruit) of Underutilized Tropical Fruit Extracts. Applied Biochemistry and Biotechnology, 175(7), 3231–3243. doi:10.1007/s12010-015-1499-0.

Hidayati, A. R., Widyawaruyanti, A., Ilmi, H., Tanjung, M., Widiandani, T., Siswandono S, S., Syafruddin, D., & Hafid, A. F. (2020). Antimalarial Activity of Flavonoid Compound Isolated from Leaves of Artocarpus altilis. Pharmacognosy Journal, 12(4), 835–842. doi:10.5530/pj.2020.12.120.

Bailly, C. (2021). Anticancer mechanism of artonin E and related prenylated flavonoids from the medicinal plant Artocarpus elasticus. Asian Journal of Natural Product Biochemistry, 19(2), 44–56. doi:10.13057/biofar/f190202.

Hafid, A. F., Aoki-Utsubo, C., Permanasari, A. A., Adianti, M., Tumewu, L., Widyawaruyanti, A., Wahyuningsih, S. P. A., Wahyuni, T. S., Lusida, M. I., Soetjipto, & Hotta, H. (2017). Antiviral activity of the dichloromethane extracts from Artocarpus heterophyllus leaves against hepatitis C virus. Asian Pacific Journal of Tropical Biomedicine, 7(7), 633–639. doi:10.1016/j.apjtb.2017.06.003.

Vázquez-González, Y., Ragazzo-Sánchez, J. A., & Calderón-Santoyo, M. (2020). Characterization and antifungal activity of jackfruit (Artocarpus heterophyllus Lam.) leaf extract obtained using conventional and emerging technologies. Food Chemistry, 330, 127211. doi:10.1016/j.foodchem.2020.127211.

Nomura, T., Hano, Y., & Aida, M. (1998). Isoprenoid-substituted flavonoids from Artocarpus plants (moraceae). Heterocycles, 47(2), 1179–1205. doi:10.3987/REV-97-SR(N)9.

Mutha, R. E., Tatiya, A. U., & Surana, S. J. (2021). Flavonoids as natural phenolic compounds and their role in therapeutics: an overview. Future Journal of Pharmaceutical Sciences, 7(1), 25. doi:10.1186/s43094-020-00161-8.

Trader, D. J., & Carlson, E. E. (2012). Chemoselective hydroxyl group transformation: An elusive target. Molecular BioSystems, 8(10), 2484–2493. doi:10.1039/c2mb25122a.

Ahmed, Q. U., Sarian, M. N., So’ad, S. Z. M., Latip, J., Ichwan, S. J. A., Hussein, N. N., Taher, M., Alhassan, A. M., Hamidon, H., & Fakurazi, S. (2018). Methylation and acetylation enhanced the antidiabetic activity of some selected flavonoids: In vitro, molecular modelling and structure activity relationship-based study. Biomolecules, 8(4), 149. doi:10.3390/biom8040149.

Sakao, K., & Hou, D. X. (2020). Effects and Mechanisms of Acylated Flavonoid on Cancer Chemopreventive Activity. Current Pharmacology Reports, 6(5), 286–305. doi:10.1007/s40495-020-00233-6.

Alley, M. C., Scudiero, D. A., Monks, A., Hursey, M. L., Czerwinski, M. J., Fine, D. L., ... & Boyd, M. R. (1988). Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Research, 48(3), 589-601.

Suhartati, T., Hernawan, Suwandi, J. F., Yandri, & Hadi, S. (2018). Isolation of Artonin E From the Root Bark of Artocarpus Rigida, Synthesis of Artonin E Acetate and Evaluation of Anticancer Activity. Macedonian Journal of Chemistry and Chemical Engineering, 37(1), 35–42. doi:10.20450/mjcce.2018.1406.

Hakim, E. H., Marlina, E. E., Mujahidin, D., Achmad, S. A., Ghisalberti, E. L., & Makmur, L. (1998). Artocarpin and heteroflavanon-A, two bioactive flavonoid compounds from Artocarpus champeden. Proceedings ITB. 30(1), 31-36.

Full Text: PDF

DOI: 10.28991/ESJ-2023-07-03-05


  • There are currently no refbacks.

Copyright (c) 2023 Tati Suhartati, Khalimatus Sa’diah, Yandri Yandri, Sutopo Hadi