Triterpenoids from Stem Bark of  Dysoxylum excelsum  and Their Cytotoxic Activity against MCF-7 Breast Cancer Cells

Sylvia Rachmawati Meilanie; Tri Mayanti; Nurlelasari Nurlelasari; Desi Harneti Putri Huspa; Rani Maharani; Achmad Zainuddin; Darwati Darwati; Euis Julaeha; Unang Supratman; Jamaludin Al Anshori

doi:10.22146/ijc.73616

Triterpenoids from Stem Bark of Dysoxylum excelsum and Their Cytotoxic Activity against MCF-7 Breast Cancer Cells

https://doi.org/10.22146/ijc.73616

Sylvia Rachmawati Meilanie⁽¹⁾, Tri Mayanti⁽²⁾, Nurlelasari Nurlelasari⁽³⁾, Desi Harneti Putri Huspa⁽⁴⁾, Rani Maharani⁽⁵⁾, Achmad Zainuddin⁽⁶⁾, Darwati Darwati⁽⁷⁾, Euis Julaeha⁽⁸⁾, Unang Supratman⁽⁹⁾, Jamaludin Al Anshori^(10*)

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(4) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(5) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(6) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(7) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(8) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(9) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia; Central Laboratory of Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(10) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(*) Corresponding Author

Abstract

The diversity of structures of triterpenoids provides a variety of interesting pharmacological effects, one of them being anticancer. Sources of triterpenoids are found in Dysoxylum excelsum, it is still rarely studied, and it potentially contains triterpenoids with cytotoxic activity. Therefore, the research aimed to isolate the triterpenoids from the stem bark of D. excelsum and determine their cytotoxic efficacy against the breast cancer cells of MCF-7. The dried stem bark of D. excelsum was macerated using methanol and then fractionated with n-hexane and ethyl acetate to obtain the corresponding fractions. Two triterpenoids, 3α,7α-dihydroxyapotirucalla-14,24-Z-dien-26-oic acid (1) and masticadienonic acid or 3-oxo-tirucalla-7,24-Z-dien-26-oic acid (2) were isolated in the first place from the Dysoxylum genus. Compounds 1 and 2 were assayed for their cytotoxic potency anti- MCF-7 using the MTT assay and gave moderate IC₅₀ values of 60.87 and 72.86 µM, respectively. Based on their analogs, partial structure modification of the compounds might increase the activity; thus, it can be further utilized as better lead compounds for anticancer drugs candidate.

Keywords

Dysoxylum excelsum; triterpenoids; Meliaceae; cytotoxic; MCF-7 breast cancer

Full Text:

Full Text PDF Full Text PDF-Suppl. Data

References

[1] Naini, A.A., Mayanti, T., Nurlelasari, N., Harneti, D., Maharani, R., Safari, A., Hidayat, A.T., Farabi. K., Lesmana, R., Supratman, U. and Shiono, Y., 2022, Cytotoxic sesquiterpenoids from Dysoxylum parasiticum (Osbeck) Kosterm. stem bark, Phytochem. Lett., 47, 102–106.

[2] Saravanan, R., Arvind, D.P., and Sujana, K.A., 2014, Dysoxylum (Blume) – New generic record to Odisha, India, Int. J. Adv. Res., 2 (8), 543–545.

[3] Kumar, V., Gupta, M., Gandhi, S.G., Bharate, S.S., Kumar, A., Vishwakarma, R.A., and Bharate, S.B., 2017, Anti-inflammatory chromone alkaloids and glycoside from Dysoxylum binectariferum, Tetrahedron Lett., 58 (42), 3974–3978.

[4] Kumara, P.M., Zuehlke, S., Priti, V., Ramesha B.T., Shweta, S., Ravikanth, G., Vasudeva, R., Santhoshkumar, T.R., Spiteller, M., and Shaanker, R.U., 2012, Fusarium proliferatum, an endophytic fungus from Dysoxylum binectariferum Hook.f, produces rohitukine, a chromane alkaloid possessing anti-cancer activity, Antonie van Leeuwenhoek, 101 (2), 323–329.

[5] Zhou, B., Shen, Y., Wu, Y., Leng, Y., and Yue, J.M., 2015, Limonoids with 11β-hydroxysteroid dehydrogenase type 1 inhibitory activities from Dysoxylum mollissimum, J. Nat. Prod., 78 (8), 2116–2122.

[6] Xu, J., Ni, G., Yang, S., and Yue, J., 2013, Dysoxylumins A–F: Six new limonoids from Dysoxylum mollissimum Bl, Chin. J. Chem., 31 (1), 72–78.

[7] Tang, T., Liao, S.G., Na, Z., Li, Y., and Xu, Y.K., 2012, Dysoxylentin A, the first 21-nortriterpenoid bearing a 2-(propan-2-ylidenyl)furan-3(2H)-one, from Dysoxylum lenticellatum, Tetrahedron Lett., 53 (9), 1183–1185.

[8] Yan, H.J., Wang, J.S., and Kong, L.Y., 2014, Cytotoxic steroids from the leaves of Dysoxylum binectariferum, Steroids, 86, 26–31.

[9] Liu, H.B., Zhang, C.R., Dong, S.H., Yang, S.P., Sun, Q., Geng, M.Y., and Yue, J.M., 2012, Sesquiterpenes from Dysoxylum oliganthum and Dysoxylum excelsum, J. Asian Nat. Prod. Res., 14 (3), 224–234.

[10] Liu, W.X., Tang, G.H., He, H.P., Zhang, Y., Li, S.L., and Hao, X.J., 2012, Limonoids and triterpenoids from the twigs and leaves of Dysoxylum hainanense, Nat. Prod. Bioprospect., 2 (1), 29–34.

[11] Dharmayani, N.K.T., Yoshimura, T., Hermawati, E., Juliawaty, L.D., and Syah, Y.M., 2020, Antibacterial and antifungal two phenolic sesquiterpenes from Dysoxylum densiflorum, Z. Naturforsch., C: Biosci., 75, 1–5.

[12] Gu, J., Cheng, G.G., Qian, S.Y., Li, Y., Liu, Y.P., and Luo, X.D., 2014, Dysoxydensins A–G, seven new clerodane diterpenoids from Dysoxylum densiflorum, Planta Med., 80 (12), 1017–1022.

[13] Zhang, P., Lin, Y., Wang, F., Fang, D., and Zhang, G., 2019, Diterpenes from Dysoxylum lukii Merr., Phytochem. Lett., 29, 53–56.

[14] Zhao, J.X., Yu, Y.Y., Wang, S.S., Huang, S.L., Shen, Y., Gao, X.H., Sheng, L., Li, J.Y., Leng, Y., Li, J., and Yue, J.M., 2018, Structural elucidation and bioinspired total syntheses of ascorbylated diterpenoid hongkonoids A-D, J. Am. Chem. Soc., 140 (7), 2485–2492.

[15] Huang, R., Zhao, Y., Wang, Y., Zhou, L., Chen, Y.F., and Wang, J.F., 2017, Cytotoxic ring A-seco triterpenoids from the stem bark of Dysoxylum lukii, J. Asian Nat. Prod. Res., 20 (9), 860–866.

[16] Yan, H., Wang, J., and Kong, L., 2014, Cytotoxic dammarane-type triterpenoids from the stem bark of Dysoxylum binecteriferum, J. Nat. Prod., 77 (2), 234−242.

[17] Zou, Y.H., Liu, W.T., Zhang, J.X., and Xiang, D.C., 2017, Triterpenoids from the bark of Dysoxylum hainanense and their anti-inflammatory and radical scavenging activity, Fitoterapia, 121, 159–163.

[18] Yan, H.J., Si, H.L., Zhao, H.W., Chen, L., Yu, J.Q., Zhao, H.Q., and Wang, X., 2021, Four new cycloartane triterpenoids from the leaves of Dysoxylum binectariferum, Phytochem. Lett., 41, 101–105.

[19] Wang, F., and Guan, Y., 2012, Cytotoxic nor-dammarane triterpenoids from Dysoxylum hainanense, Fitoterapia, 83 (1), 13–17.

[20] Fujioka, T., Sakurai, A., Mihashi, K., Kashiwada, Y., Chen, I.S., and Lee, K.H., 1997, Antitumor agents. 169. Dysoxylum cumingianum V. Cumingianosides P and Q, new cytotoxic triterpene glucosides with an apotirucallane-type skeleton from Dysoxylum cumingianum, Chem. Pharm. Bull., 45 (1), 202–206.

[21] Kumar, V., Bharate, S.S., Bhurta, D., Gupta, M., Gandhi, S.G., Singh, D., Jaglan, S., Kumar, A., Vishwakarma, R.A., and Bharate, S.B., 2020, Evaluation of rohitukine-enriched fraction of Dysoxylum binectariferum Hook.f. (leaves) as anti-arthritic phytopharmaceutical candidate: Chemical standardization, in-vivo validation, formulation development and oral pharmacokinetics, J. Ethnopharmacol., 254, 112758.

[22] Jiang, K., Chen, L.L., Wang, S.F., Wang, Y., Li, Y., and Gao, K., 2015, Antiinflammatory terpenoids from the leaves and twigs of Dysoxylum gotadhora, J. Nat. Prod., 78 (5), 1037–1044.

[23] Hu, J., Song, Y., Li, H., Yang, B., Mao, X., Zhao, Y., and Shi, X., 2014, Cytotoxic and anti-inflammatory tirucallane triterpenoids from Dysoxylum binectariferum, Fitoterapia, 99, 86–91.

[24] Cao, P., Liang, G., Gao, X., Wang, X., and Li, Z., 2013, Three new nor-dammarane triterpenoids from Dysoxylum hainanense with particular cytotoxicity against glioma cell line, Arch. Pharmacal Res., 36 (3), 322–326.

[25] De Los Reyes, M.M., Oyong, G.G., Ng, V.A.S., Shen, C.C., and Ragasa, C.Y., 2016, Cytotoxic compounds from Dysoxylum gaudichaudianum (A. Juss.) Miq., Int. J. Pharmacogn. Phytochem. Res., 8 (4), 663–667.

[26] Han, L.M., Zhao, J.X., Liu, H.C., Ni, G., Ding, J., Yang, S.P., and Yue, J.M., 2015, Limonoid and triterpenoids from Dysoxylum mollissimum var. glaberrimum, J. Nat. Prod., 78 (4), 754–761.

[27] Ragasa, C.Y., Ng, V.A.S., De Los Reyes, M.M., Mandia, E.H., Oyong, G.G., and Shen, C.C., 2014, Chemical constituent and cytotoxic of the leaves of Dysoxylum gaudichaudianum (A. Juss.) Miq., Pharma Chem., 6 (5), 182–187.

[28] Pham, N.K., Bui, H.T., Tran, T.H., Hoang, T.N.A., Vu, T.H., Do, D.T., Kim, Y.H., Song, S.B., To, D.C., and Nguyen, M.C., 2021, Dammarane triterpenes and phytosterols from Dysoxylum tpongense Pierre and their anti-inflammatory activity against liver X receptors and NF-κB activation, Steroids, 175, 108902.

[29] Gopalakrishnan, S., Lakshmi, S.Y.S., and Banu, F., 2015, Comparison of antimicrobial activities of silver nanoparticle synthesized from Dysoxylum parasiticum, Indian J. Med. Healthcare, 4 (2), 1–5.

[30] Dharmayani, N.K.T., Juliawaty, L.D., and Syah, Y.M., 2016, Three tetracyclic triterpenoic acids from Dysoxylum densiflorum and their antibacterial activities, Nat. Prod. Commun., 11 (8), 1081–1083.

[31] Hu, J., Song, Y., Li, H., Mao, X., Zhao, Y., Shi, X., and Yang, B., 2014, Antibacterial and cytotoxic triterpenoids from the ethanol extract of Dysoxylum densiflorum (Blume) Miq., Phytochem. Lett., 10, 219–223.

[32] Soepadmo, E., and Saw, L.G., 2002, Tree Flora of Sabah and Sarawak, Volume 3, 4^th Ed., Sabah Forestry Department, Forest Research Institute Malaysia (FRIM), Sarawak Forestry Department, Malaysia.

[33] Zainuddin, A., Meilanie, S.R., Darwati, D., Kurniawan, K., Nurlelasari, N., Herlina, T., Saputra, A.D., Al Anshori, J., and Mayanti, T., 2020, Cytotoxic triterpenoids from the stem barks of Dysoxylum arborescens and Dysoxylum excelsum against MCF-7 breast cancer cell, Sains Malays., 49 (5), 989–994.

[34] Mehmood, A., Malik, A., Anis, I., Khan, P.M., Riaz, M., Makhmoor, T., and Choudhary, M.I., 2010, Highly oxygenated triterpenes from the roots of Atropa acuminata, Nat. Prod. Lett., 16 (6), 371–376.

[35] Krasteva, I., Jenett-Siems, K., Kaloga, M., and Nikolov, S., 2009, 3-O-Sulfo-triterpenoid Saponins from Gypsophila trichotoma Wend, Z. Naturforsch., B: Chem. Sci., 64 (3), 319–322.

[36] Supratman, U., Naibaho, W., Salam, S., Maharani, R., Hidayat, A.T., Harneti, D., Nurlelasari, N., and Shiono, Y., 2019, Cytotoxic Triterpenoids from the Bark of Chisocheton patens Blume (Meliaceae), Phytochem. Lett., 30, 81–87.

[37] Wang, L.Y., Wang, N.L., Yao, X.S., Miyata, S., and Kitanaka, S., 2003, Euphane and tirucallane triterpenes from the roots of Euphorbia kansui and their in vitro effects on the cell division of Xenopus, J. Nat. Prod., 66 (5), 630–633.

[38] Mulholland, D.A., and Nair, J.J., 1994, Triterpenoids from Dysoxylum pettigrewianum, Phytochemistry, 37 (5), 1409–1411.

[39] Kuete, V., and Efferth, T., 2015, African flora has the potential to fight multidrug resistance of cancer, BioMed Res. Int., 2015, 914813.

[40] Naini, A.A., Mayanti, T., and Supratman, U., 2022, Triterpenoids from Dysoxylum genus and their biological activities, Arch. Pharmacal Res., 45 (2), 63–89.

[41] Nugroho, A.E., Momota, T., Sugiura, R., Hanzawa, M., Yajima, E., Nagakura, Y., Yasuda, N., Hirasawa, Y., Wong, C.P., Kaneda, T., Hadi, A.H.A., Fukaya, H., and Morita, H., 2014, Dysotriflorins A–M, triterpenoids from Dysoxylum densiflorum, Tetrahedron, 70 (51), 9661–9667.

[42] Prakash, O., Ahmad, A., Tripathi, V.K., Tandon, S., and Pant, A.B., 2014, In silico assay development for screening of tetracyclic triterpenoids as anticancer agents against human breast cancer cell line MCF7, PLoS ONE, 9 (11), e111049.

DOI: https://doi.org/10.22146/ijc.73616