Citation: Farabi, K.; Harneti, D.; Darwati; Mayanti, T.; Nurlelasari; Maharani, R.; Sari, A.P.; Herlina, T.; Hidayat, A.T.; Supratman, U.; et al. Dammarane-Type Triterpenoid from the Stem Bark of Aglaia elliptica (Meliaceae) and Its Cytotoxic Activities. Molecules 2022, 27, 6757. https://doi.org/10.3390/molecules 27196757 Academic Editor: Junho Kim Received: 16 September 2022 Accepted: 8 October 2022 Published: 10 October 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). molecules Article Dammarane-Type Triterpenoid from the Stem Bark of Aglaia elliptica (Meliaceae) and Its Cytotoxic Activities Kindi Farabi 1 , Desi Harneti 1 , Darwati 1 , Tri Mayanti 1 , Nurlelasari 1 , Rani Maharani 1,2 , Aprilia Permata Sari 1 , Tati Herlina 1 , Ace Tatang Hidayat 1,2 , Unang Supratman 1,2, *, Sofa Fajriah 3 , Mohamad Nurul Azmi 4 and Yoshihito Shiono 5 1 Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor 45363, Indonesia 2 Central Laboratory of Universitas Padjadjaran, Jatinangor 45363, Indonesia 3 Research Center for Chemistry, National Research and Innovation Agency (BRIN) Kawasan PUSPIPTEK Serpong, South Tangerang 15314, Indonesia 4 School of Chemical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia 5 Department of Food, Life, and Environmental Science, Faculty of Agriculture, Yamagata University, Tsuruoka 997-8555, Japan * Correspondence: unang.supratman@unpad.ac.id; Tel.: +62-22-7794391 Abstract: Two new dammarane-type triterpenoid fatty acid ester derivatives, 3β-oleate-20S-hydroxy- dammar-24-en (1) and 3β-oleate-20S,24S-epoxy-25-hydroxydammarane (2) with a known dammarane- type triterpenoid compound, such as 20S-hydroxydammar-24-en-3-on (3), were isolated from the stem bark of Aglaia elliptica (C.DC.) Blume. The chemical structures were determined by spectroscopic methods, including FTIR, NMR (one and two-dimensional), and HRESITOF-MS analysis, as well as chemical derivatization and comparison with previous literature. Furthermore, the synthetic analog resulting from transesterification of 1 and 2 also obtained 3β,20S-dihydroxy-dammar-24-en (4) and 20S,24S-epoxy-3β,25-dihydroxydammarane (5), respectively. The cytotoxic effect of all isolated and synthetic analog compounds was evaluated using PrestoBlue reagent against MCF-7 breast cancer cell and B16-F10 melanoma cell lines. The 20S-hydroxydammar-24-en-3-on (3) showed the strongest activity against MCF-7 breast cancer and B16-F10 melanoma cell, indicating that the ketone group at C-3 in 3 plays an essential role in the cytotoxicity of dammarane-type triterpenoid. On the other hand, compounds 1 and 2 had very weak cytotoxic activity against the two cell lines, indicating the presence of fatty acid, significantly decreasing cytotoxic activity. This showed the significance of the discovery to investigate the essential structural feature in dammarane-type triterpenoid, specifically for the future development of anticancer drugs. Keywords: dammarane-type triterpenoid fatty acid ester; Aglaia elliptica; cytotoxic activity; MCF-7 cell line; B16-F10 cell line 1. Introduction The Aglaia is the largest genus of the Meliaceae family, consisting of 150 species mainly distributed in tropical and sub-tropical regions such as Asia, Northern Australia, and the Pacific. Furthermore, approximately 65 species grow in Indonesia [1,2]. This plant is used traditionally in the country to treat wounds, fever, and skin disease [3]. On the other hand, phytochemical research of Aglaia genus revealed a number of diterpenoids [4,5], triterpenoids [6,7], sesquiterpenoids [8,9], limonoids [10,11], steroids [12], flavaglines [13], bisamides [14], and lignans [15,16]. The biological activity of the extracts and secondary metabolites includes cytotoxic [17,18], insecticidal [19], anti-inflammatory [5], antifun- gal [20], and molluscicide [21]. Dammarane triterpenoid is one of the secondary metabolite groups commonly dis- covered in the Aglaia genus. Approximately 29 dammarane-type triterpenoids have been Molecules 2022, 27, 6757. https://doi.org/10.3390/molecules27196757 https://www.mdpi.com/journal/molecules