Cancer is a major health issue around the globe. Chemotherapy and radiation therapy are no longer the standard treatments for patients as these remedies lead to many adverse effects. Thus, the development of alternative effective drugs from lead compounds, especially natural products is necessary. This study aimed to isolate cytotoxic phytochemical constituents from a plant Calophyllum inophyllum, which has been used as traditional medicine since ancient time. The root of C. inophyllum was extracted and subjected for phytochemical constituent isolation. A coumarin, benjaminin (1) was isolated successfully from the chloroform extract and its structural elucidation was performed by spectroscopy analyses of MS, IR and NMR. The anti-proliferative effect of 1 on four cancer cell lines, leukemia (K562), stomach (SNU-1), liver (Hep-G2) and lung (NCI-H23) cancers were evaluated by using colorimetric MTT assay. Benjaminin (1) exhibited cytotoxic effects towards all cancer cells and showed the strongest inhibition towards SNU-1 cell proliferation with an IC50 value of 70.42 μM. The outcome of this study revealed that 1 is a potential cytotoxic lead compound that could be further developed into anti-cancer drug. Thus, the study on the structure-activity relationship of 1 is highly recommended in due course to improve its anti-proliferative effects on cancer cells.
Alkhamaiseh, S.I., Taher, M., Ahmad, F., Qaralleh, H., Althunibat, O.Y., Susanti, D. & Ichwan, S.J.A. (2012). The phytochemical content and antimicrobial activities of Malaysian Calophyllum canum (stem bark). Pakistan Journal of Pharmaceutical Sciences, 25, 555-563.
Alkhamaiseh, S.I., Taher, M., Ahmad, F., Susanti, D., Jauhari, S. & Ichwan, A. (2011). Antioxidant and cytotoxic activities of Calophyllum rubiginosum. International Journal of Phytomedicine, 3, 157-163.
Ee, G.C.L., Mah, S.H., Teh, S.S., Rahmani, M., Go, R. & Taufiq-Yap, Y.H. (2011). Soulamarin, a new coumarin from stem bark of Calophyllum soulattri. Molecules, 16, 9721-9727.
Guilet, D., Seraphin, D., Rondeau, D., Richomme, P. & Bruneton, J. (2001a). Cytotoxic coumarins from Calophyllum dispar. Phytochemistry, 58, 571-575.
Guilet, D., Helesbeux, J.J., Seraphin, D., Sevenet, T., Richomme, P. & Bruneton, J. (2001b). Novel cytotoxic 4-phenylfuranocoumarins from Calophyllum dispar. Journal of Natural Products, 64, 563-568.
Ito, C., Itoigawa, M., Furukawa, H., Tokuda, H., Okuda, Y., Mukainaka, T., Okuda, M. & Nishino, H. (1999). Anti-tumor-promoting effects of 8-substituted 7-methoxycoumarins on Epstein-Barr virus activation assay. Cancer Letters, 138, 87-92.
Itoigawa, M., Ito, C., Tan, H.T., Kuchide, M., Tokuda, H., Nishino, H. & Furukawa, H. (2001). Cancer chemopreventive agents, 4-phenylcoumarins from Calophyllum inophyllum. Cancer Letters, 169, 15-19.
Khan, M.R., Kihara, M. & Omoloso, A.D. (2002). Antimicrobial activity of Calophyllum soulattri. Fitoterapia, 73, 741-743.
Mah, S.H., Ee, G.C.L. & Teh, S.S. (2013). Chemistry and cytotoxic activity of essential oil from the stem bark of Calophyllum soulattri. Asian Journal of Chemistry, 25, 8831-8832.
McKee, T.C., Fuller, R.W., Covington, C.D., Cardellina, J.H., Gulakowski, R.J., Krepps, B.L., McMahon, J.B. & Boyd, M.R. (1996). New pyranocoumarins isolated from Calophyllum lanigerum and Calophyllum teysmannii. Journal of Natural Products, 59, 754-758.
Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survivals: Application to proliferation and cytotoxic assays. Journal of Immunological Methods, 65, 55-63.
Reyes-Chilpa, R., Estrada-Muniz, E., Apan, T.R., Amekraz, B., Aumelas, A., Jankowski, C.K. & Vazquez- Torres, M. (2004). Cytotoxic effects of mammea type coumarins from Calophyllum brasiliense. Life Sciences, 75, 1635-47.
Sahimi, M.S.M., Ee, G.C.L., Mahaiyiddin, A.G., Daud, S., Teh, S.S., See, I. & Sukari, M.A. (2015). A new natural product compound Benjaminin from Calophyllum benjaminum. Pertanika Journal of Tropical Agricultural Science, 38, 1-6.
Souza, M.D.O.C., Beserra, A.M., Martins, D.C., Real, V.V., Santos, R.A., Rao, V.S., Silva, R.M. & Martins, D.T. (2009). In vitro and in vivo anti-Helicobacter pylori activity of Calophyllum brasiliense Camb. Journal of Ethnopharmacology, 123, 452-428.
Spino, C., Dodier, M. & Sotheeswaran, S. (1998). Anti- HIV coumarins from Calophyllum seed oil. Bioorganic & Medicinal Chemistry Letters, 8, 3475-3478.
Tsai, S.C., Liang, Y.H., Chiang, J.H., Liu, F.C., Lin, W.H., Chang, S.J., Lin, W.Y., Wu, C.H. & Weng, J.R. (2012). Anti-inflammatory effects of Calophyllum inophyllum L. in RAW264.7 cells. Oncology Reports, 28, 1096-1102.
Verotta, L., Lovaglio, E., Vidari, G., Finzi, P.V., Neri, M.G., Raimondi, A., Parapini, S., Taramelli, D. & Riva, A. (2004). Bombardelli E. 4-Alkyl- and 4-phenylcoumarins from Mesua ferrea as promising multidrug resistant antibacterials. Phytochemistry, 65, 2867-2879.
Win, N.N., Awale, S., Esumi, H., Tezuka, Y. & Kadota, S. (2008). Novel anticancer agents, kayeassamins C-I from the flower of Kayea assamica of Myanmar. Bioorganic & Medicinal Chemistry, 16, 8653-8660.
Mah, Siau Hui; Teh, Soek Sin; Ismail, Ahmad Azri Fitri; and Ee, Gwendoline Cheng Lian
"Anti-proliferative Effects of a Coumarin Benjaminin on Four Human Cancer Cell Lines,"
Pharmaceutical Sciences & Research: Vol. 7
, Article 7.
Available at: https://scholarhub.ui.ac.id/psr/vol7/iss1/7