Sesquiterpenoids from  Dysoxylum amooroides  Stem Bark: Isolation, Structure Determination, and Cytotoxicity Against MCF-7 Breast Cancer Cells

Latifah Gunawan; Hidayat Nurul Mustofa; Al Arofatus Naini; Desi Harneti; Ace Tatang Hidayat; Nurlelasari Nurlelasari; Rani Maharani; Tri Mayanti; Sofa Fajriah; Khalijah Awang; Mohamad Nurul Azmi; Unang Supratman

doi:10.22146/ijc.99121

Sesquiterpenoids from Dysoxylum amooroides Stem Bark: Isolation, Structure Determination, and Cytotoxicity Against MCF-7 Breast Cancer Cells

https://doi.org/10.22146/ijc.99121

Latifah Gunawan⁽¹⁾, Hidayat Nurul Mustofa⁽²⁾, Al Arofatus Naini⁽³⁾, Desi Harneti⁽⁴⁾, Ace Tatang Hidayat⁽⁵⁾, Nurlelasari Nurlelasari⁽⁶⁾, Rani Maharani⁽⁷⁾, Tri Mayanti⁽⁸⁾, Sofa Fajriah⁽⁹⁾, Khalijah Awang⁽¹⁰⁾, Mohamad Nurul Azmi⁽¹¹⁾, Unang Supratman^(12*)

(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) Research Center for Chemistry, National Research and Innovation Agency (BRIN), Jl. Kw. Puspiptek, Muncul, Kawasan PUSPIPTEK Serpong, Tangerang Selatan 15314, 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; Central Laboratory of 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) Research Center for Chemistry, National Research and Innovation Agency (BRIN), Jl. Kw. Puspiptek, Muncul, Kawasan PUSPIPTEK Serpong, Tangerang Selatan 15314, Indonesia
(10) Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia
(11) School of Chemical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia
(12) 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
(*) Corresponding Author

Abstract

Three sesquiterpenoids, guaianediol (1), alismol (2), and spathulenol (3), were isolated from the n-hexane and ethyl acetate extracts of the stem bark of Dysoxylum amooroides. The three compounds were found in D. amooroides species for the first time. The structures of the isolated compounds were identified and established based on an extensive spectroscopic analysis involving HR-TOF-ESI-MS, IR, and NMR data, as well as a comparison with the previously reported works of literature. Compounds 1-3 were further assessed for cytotoxic effects against MCF-7 breast cancer cells. Guaianediol (1) showed inactive activity with IC₅₀ > 100 µM, alismol (2) showed weak activity with IC₅₀ value of 82.1 µM and spathulenol (3) showed considerable activity with an IC₅₀ value of 15.2 µM. A brief structure-activity relationship and comparison with the previous works were also discussed to understand better the role of guaiane- and aromadendrane-type sesquiterpenoids in the biological activity perspective.

Keywords

cytotoxic activity; Dysoxylum amooroides; MCF-7; sesquiterpenoids

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References

[1] Çelik, K., Toǧar, B., Türkez, H., and Taşpinar, N., 2014, In vitro cytotoxic, genotoxic, and oxidative effects of acyclic sesquiterpene farnesene, Turk. J. Biol., 38 (2), 253–259.

[2] Davis, E.M., and Croteau, R., 2000, “Cyclization Enzymes in the Biosynthesis of Monoterpenes, Sesquiterpenes, and Diterpenes” in Biosynthesis: Aromatic Polyketides, Isoprenoids, Alkaloids, Eds. Leeper, F.J., and Vederas, J.C., Springer Berlin, Heidelberg, Germany, 53–92.

[3] Avalos, M., Garbeva, P., Vader, L., van Wezel, G.P., Dickschat, J.S., and Ulanova, D., 2022, Biosynthesis, evolution and ecology of microbial terpenoids, Nat. Prod. Rep., 39 (2), 249–272.

[4] Wang, M., Zhao, L., Chen, K., Shang, Y., Wu, J., Guo, X., Chen, Y., Liu, H., Tan, H., and Qiu, S.X., 2020, Antibacterial sesquiterpenes from the stems and roots of Thuja sutchuenensis, Bioorg. Chem., 96, 103645.

[5] Perveen, S., Alqahtani, J., Orfali, R., Aati, H.Y., Al-Taweel, A.M., Ibrahim, T.A., Khan, A., Yusufoglu, H.S., Abdel-Kader, M.S., and Taglialatela-Scafati, O., 2020, Antibacterial and antifungal sesquiterpenoids from aerial parts of Anvillea garcinii, Molecules, 25 (7), 1730.

[6] Han, L., Zheng, W., Qian, S.Y., Yang, M.F., Lu, Y.Z., He, Z.J., and Kang, J.C., 2023, New guaiane-type sesquiterpenoids biscogniauxiaols A–G with anti-fungal and anti-inflammatory activities from the endophytic fungus Biscogniauxia petrensis, J. Fungi, 9 (4), 393.

[7] Wu, C.C., Huang, S.L., Ko, C.H., and Chang, H.T., 2022, Antifungal sesquiterpenoids from Michelia formosana leaf essential oil against wood-rotting fungi, Molecules, 27 (7), 2136.

[8] Kim, T.H., Hatano, T., Okamoto, K., Yoshida, T., Kanzaki, H., Arita, M., and Ito, H., 2017, Antifungal and ichthyotoxic sesquiterpenoids from Santalum album heartwood, Molecules, 22 (7), 1139.

[9] Misra, H., Mehta, D., Mehta, B.K., and Jain, D.C., 2014, Extraction of artemisinin, an active antimalarial phytopharmaceutical from dried leaves of Artemisia annua L., using microwaves and a validated HPTLC-visible method for its quantitative determination, Chromatogr. Res. Int., 2014 (1), 361405.

[10] de Cássia Da Silveira e Sá, R., Andrade, L.N., and De Sousa, D.P., 2015, Sesquiterpenes from essential oils and anti-inflammatory activity, Nat. Prod. Commun., 10 (10), 1767–1774.

[11] Lee, Y.K., Lee, H., Kim, Y.N., Kang, J., Jeong, E.J., and Rho, J.R., 2023, Sesquiterpene lactones with anti-inflammatory activity from the halophyte Sonchus brachyotus DC, Molecules, 28 (4), 1518.

[12] Paço, A., Brás, T., Santos, J.O., Sampaio, P., Gomes, A.C., and Duarte, M.F., 2022, Anti-inflammatory and immunoregulatory action of sesquiterpene lactones, Molecules, 27 (3), 1142.

[13] Li, J., Li, X., Wang, X., Zhong, X., Ji, L., Guo, Z., Liu, Y., and Shang, X., 2019, Sesquiterpenoids and their anti-inflammatory activity: Evaluation of Ainsliaea yunnanensis, Molecules, 24 (9), 1701.

[14] Hai, C.T., Luyen, N.T., Giang, D.H., Minh, B.Q., Trung, N.Q., Chinh, P.T., Hau, D.V., and Dat, N.T., 2023, Atractylodes macrocephala rhizomes contain anti-inflammatory sesquiterpenes, Chem. Pharm. Bull., 71 (6), 451–453.

[15] Riyadi, S.A., Naini, A.A., and Supratman, U., 2023, Sesquiterpenoids from Meliaceae family and their biological activities, Molecules, 28 (12), 4874.

[16] Boudermine, S., Parisi, V., Lemoui, R., Boudiar, T., Chini, M.G., Franceschelli, S., Pecoraro, M., Pascale, M., Bifulco, G., Braca, A., De Tommasi, N., and De Leo, M., 2022, Cytotoxic sesquiterpenoids from Ammoides atlantica aerial parts, J. Nat. Prod., 85 (3), 647–656.

[17] Zaghloul, A.M., Yusufoglu, H.S., Salkini, M.A.A., and Alam, A., 2014, New cytotoxic sesquiterpene lactones from Anthemis scrobicularis, J. Asian Nat. Prod. Res., 16 (9), 922–929.

[18] El Feky, S.E., Abd El Hafez, M.S.M., Abd El Moneim, N.A., Ibrahim, H.A.H., Okbah, M.A., Ata, A., El Sedfy, A.S., and Hussein, A., 2022, Cytotoxic and antimicrobial activities of two new sesquiterpenoids from red sea brittle star Ophiocoma dentata, Sci. Rep., 12 (1), 8209.

[19] Jang, H.J., Kim, J.H., Oh, H.M., Kim, M.S., Jo, J.H., Jung, K., Lee, S., Kim, Y.H., Lee, W.S., Lee, S.W., and Rho, M.C., 2016, Sesquiterpenoids from the rhizomes of Curcuma phaeocaulis and their inhibitory effects on LPS-induced TLR4 activation, Chem. Pharm. Bull., 64 (7), 1062–1066.

[20] Izdihar, G., Naini, A. A., Harneti, D., Maharani, R., Nurlelasari, N., Safari, A., Farabi, K., Supratman, U., and Azmi, M. N., 2021, Sesquiterpenoids from the stem bark of Aglaia simplicifolia and their cytotoxic activity against B16-F10 melanoma skin cancer cell, Indones. J. Chem., 21 (6), 1560–1567.

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

[22] Parulian, S.S., Nurlelasari, N., Naini, A.A., Hilmayanti, E., Mayanti, T., Harneti, D., Darwati, D., Maharani, R., Farabi, K., Supratman, U., Anwar, R., Fajriah, S., Azmi, M.N., and Shiono, Y., 2022, Sesquiterpenoids from stem bark of Chisocheton lasiocarpus and their cytotoxic activity against MCF-7 breast cancer cell, Molekul, 17 (3), 413–420.

[23] Kouame, C., Ouattara, Z.A., Kambire, D.A., Monteil, M., Mamyrbekova, J.A., Bighelli, A., Tomi, F., Lecouvey, M., and Bekro, Y.A., 2022, Chemical composition and biological activity of Guarea cedrata (A. Chev.) Pellegr. leaf and root bark essential oil, Int. J. Biochem. Res. Rev., 31 (9), 27–35.

[24] Adeniyi, B.A., Adagbasa, O.O., Idowu, P.A., Igbokwe, C.O., Moody, J.O., and Aiyelaagbe, O.O., 2024, Extracts of Trichilia heudelotii (Meliaceae) Planch, a Nigerian medicinal plant have antibacterial and antifungal activity, J. Pharm. Res. Int., 36 (3), 24–33.

[25] Fadhilah, K., Wahyuono, S., and Astuti, P., 2021, A sesquiterpene aldehyde isolated from ethyl acetate extract of Lansium domesticum fruit peel, Indones. J. Pharm., 32 (3), 394–398.

[26] Nugroho, A.E., Sugiura, R., Momota, T., Hirasawa, Y., Wong, C.P., Kaneda, T., Hadi, A.H.A., and Morita, H., 2015, Dysosesquiflorins A and B, sesquiterpenoids from Dysoxylum densiflorum, J. Nat. Med., 69 (3), 411–415.

[27] Naini, A.A., Mayanti, T., Harneti, D., Darwati, D., Nurlelasari, N., Maharani, R., Farabi, K., Herlina, T., Supratman, U., Fajriah, S., Kuncoro, H., Azmi, M.N., Shiono, Y., Jungsuttiwong, S., and Chakthong, S., 2023, Sesquiterpenoids and sesquiterpenoid dimers from the stem bark of Dysoxylum parasiticum (Osbeck) Kosterm, Phytochemistry, 205, 113477.

[28] 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.

[29] Zhang, P.Z., Zhang, Y.M., Lin, Y., Wang, F., and Zhang, G.L., 2020, Three new diterpenes from Dysoxylum lukii and their NO production inhibitory activity, J. Asian Nat. Prod. Res., 22 (6), 531–536.

[30] Ragasa, C.Y., Torres, O.B., Bernardo, L.O., Mandia, E.H., Don, M.J., and Shen, C.C., 2013, Glabretal-type triterpenoids from Dysoxylum mollissimum, Phytochem. Lett., 6 (4), 514–518.

[31] He, X.F., Wang, X.N., Yin, S., Dong, L., and Yue, J.M., 2011, Ring A-seco triterpenoids with antibacterial activity from Dysoxylum hainanense, Bioorg. Med. Chem. Lett., 21 (1), 125–129.

[32] Bhardwaj, N., Gupta, P., Tripathi, N., Chakrabarty, S., Verma, A., Kumari, S., Gautam, V., Ravikanth, G., and Jain, S.K., 2024, New ring-A modified cycloartane triterpenoids from Dysoxylum malabaricum bark: Isolation, structure elucidation and their cytotoxicity, Steroids, 205, 109390.

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

[34] Riyadi, S.A., Naini, A.A., Mayanti, T., Lesmana, R., Azmi, M.R., Fajriah, S., Jungsuttiwong, S., and Supratman, U., 2024, Alliaxylines A-E: Five new mexicanolides from the stem barks of Dysoxylum alliaceum (Blume) Blume ex A.Juss, J. Nat. Med., 78 (3), 558–567.

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

[36] 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.

[37] Naini, A.A., Mayanti, T., Maharani, R., Harneti, D., Nurlelasari, N., Farabi, K., Fajriah, S., Hilmayanti, E., Kabayama, K., Shimoyama, A., Manabe, Y., Fukase, K., Jungsuttiwong, S., Prescott, T.A.K., and Supratman, U., 2024, Paraxylines A-G: Highly oxygenated preurianin-type limonoids with immunomodulatory TLR4 and cytotoxic activities from the stem bark of Dysoxylum parasiticum, Phytochemistry, 220, 114009.

[38] Riyadi, S.A., Naini, A.A., Mayanti, T., Farabi, K., Harneti, D., Nurlelasari, N., Maharani, R., Lesmana, R., Fajriah, S., Jungsuttiwong, S., Awang, K., Azmi, M.N., and Supratman, U., 2024, Alliaceumolide A: A rare undescribed 17-membered macrolide from Indonesian Dysoxylum alliaceum, Phytochem. Lett., 62, 73–77.

[39] Laksmi, V., Pandey, K., and Agarwal, S.K., 2009, Bioactivity of the compounds in genus Dysoxylum, Acta Ecol. Sin., 29 (1), 30–44.

[40] 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.

[41] El Sayed, K.A., and Hamann, M.T., 1996, A new norcembranoid dimer from the Red Sea soft coral Sinularia gardineri, J. Nat. Prod., 59 (7), 687–689.

[42] Peng, G.P., Tian, G., Huang, X.F., and Lou, F.C., 2003, Guaiane-type sesquiterpenoids from Alisma orientalis, Phytochemistry, 63 (8), 877–881.

[43] Khanh, P.N., Tai, B.H., Huong, T.T., Cuong, T.D., Hai, H.V., Luong, N.X., Kim, Y.H., and Cuong, N.M., 2019, Terpenoids from the leaves and stems of Dysoxylum tpongense, Vietnam J. Sci. Technol., 57 (2), 139–145.

[44] de Paiva, Y.G., Silva, T.L., Xavier, A.F.A., Cardoso, M.F.C., da Silva, F.C., Silva, M.F.S., Pinheiro, D.P., Pessoa, C., Ferreira, V.F., and Goulart, M.O.F., 2019, Relationship between electrochemical parameters, cytotoxicity data against cancer cells of 3-thio-substituted nor-beta-lapachone derivatives. Implications for cancer therapy, J. Braz. Chem. Soc., 30 (3), 658–672.

[45] Li, C., Yan, W., Cui, E., and Zheng, C., 2021, Anti-bacterial effect of phytoconstituents isolated from Alimatis rhizoma, Appl. Biol. Chem., 64 (1), 9.

[46] Viet Thanh, N.T., Minh, T.T., Thu Hien, D.T., Cuong, H.D., Seo, Y., Park, S.J., Namkung, W., Nhiem, N.X., Yen, P.H., Kim, S.H., and Kiem, P.V., 2019, Chemical constituents of Phoebe poilanei and their cytotoxic activity, Nat. Prod. Commun., 14 (5), 1934578X19850969.

[47] Kim, K.H., Kim, S., Kwun, M.J., Lee, J.Y., Oh, S.R., Choi, J.Y., and Joo, M., 2023, Alismol purified from the tuber of Alisma orientale relieves acute lung injury in mice via Nrf2 activation, Int. J. Mol. Sci., 24 (21), 15573.

[48] Dzul-Beh, A.J., García-Sosa, K., Uc-Cachón, A.H., Bórquez, J., Loyola, L.A., Barrios-García, H.B., Peña-Rodríguez, L.M., and Molina-Salinas, G.M., 2019, In vitro growth inhibition and bactericidal activity of spathulenol against drug-resistant clinical isolates of Mycobacterium tuberculosis, Rev. Bras. Farmacogn., 29 (6), 798–800.

DOI: https://doi.org/10.22146/ijc.99121