Al Arofatus Naini, Sofa Fajriah, Agus Budiawan Naro Putra, Kartika Dyah Palupi, Tri Mayanti, Unang Supratman, Kazuya Kabayama, Koichi Fukase, Siriporn Jungsuttiwong, Sutandyo Dwija Laksmana
The phytochemical investigation of the Indonesian Dysoxylum parasiticum (Osbeck) Kosterm. (Meliaceae) stem barks led to the discovery of five furofuran lignans, comprising the corrected of a known (+)-syringaresinol (1), an undescribed monomer dysoticumol A (2), and three undescribed oligomers dysoticumols B-D (3–5). The structure confirmation in 1 as a parent skeleton from bis-benzopyran to bis-benzofuran provides structural insights for the rest of four undescribed ones. The determination of their structures, encompassing absolute configurations, was established by HR-ESI-MS, NMR, X-ray diffraction analysis, ECD, quantum chemical calculation stimulated by time-dependent density functional theory (TD-DFT) approach, and statistical probability analysis (DP4+). The immunomodulatory assay showed that an unusual furofuran lignan-calamenene hybrid (3) was a potent antagonist TLR4 stimulated by LPS of both human and murine TLR4 by suppressing the NF-κB-dependent SEAP level on HEK-Blue cells and productions of pro-inflammatory cytokines TNF-α, IL-1β, IL-1α, and IL-6 on the THP-1 and RAW264.7 cells. A symmetrical furofuran lignan-ferulate oligomer (4) was found to be a partial agonist TLR4 on human receptor. Moreover, dysoticumols B (3) and D (5) showed modest cytotoxicity against human MCF-7 breast cancer and human A-549 lung cancer cells with the IC50 values between 30.4 and 48.3 μM, nothing that 5 slightly reduced inhibition against A-549 cells. Furthermore, a concise analysis of the structure-activity relationship (SAR) was provided. © 2025 Elsevier Ltd
Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency (BRIN), Cibinong Science Center Complex – BRIN, Cibinong, West Java, Bogor, 16911, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, West Java, Sumedang, 45363, Indonesia; Study Centre of Natural Product Chemistry and Synthesis, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, West Java, Sumedang, 45363, Indonesia; Central Laboratory, Universitas Padjadjaran, Jatinangor, West Java, Sumedang, 45363, Indonesia; Institute for Radiation Sciences, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043, Japan; Department of Chemistry, of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043, Japan; Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand; Integrated Laboratory, Universitas Negeri Malang, Jalan Semarang 5, Jawa Timur, Malang, 65145, Indonesia
