Paraxylines A-G: Highly oxygenated preurianin-type limonoids with immunomodulatory TLR4 and cytotoxic activities from the stem bark of Dysoxylum parasiticum.
| Autor: | Naini AA; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia; Central Laboratory, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia., Mayanti T; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia; Study Centre of Natural Product Chemistry and Synthesis, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia., Maharani R; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia; Study Centre of Natural Product Chemistry and Synthesis, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia., Harneti D; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia; Study Centre of Natural Product Chemistry and Synthesis, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia., Nurlelasari; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia; Study Centre of Natural Product Chemistry and Synthesis, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia., Farabi K; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia; Study Centre of Natural Product Chemistry and Synthesis, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia., Fajriah S; Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency (BRIN), Cibinong Science Center Complex - BRIN, Cibinong, 16911, Bogor, West Java, Indonesia., Hilmayanti E; Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043, Japan., Kabayama K; Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043, Japan., Shimoyama A; Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043, Japan., Manabe Y; Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043, Japan., Fukase K; Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043, Japan., Jungsuttiwong S; Department of Chemistry, Faculty of Science, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand., Prescott TAK; Royal Botanic Garden, Kew, Richmond, Surrey, TW9 3AB, London, United Kingdom., Supratman U; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia; Central Laboratory, Universitas Padjadjaran, Jatinangor, 45363, Sumedang, West Java, Indonesia. Electronic address: unang.supratman@unpad.ac.id. |
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| Jazyk: | angličtina |
| Zdroj: | Phytochemistry [Phytochemistry] 2024 Apr; Vol. 220, pp. 114009. Date of Electronic Publication: 2024 Feb 09. |
| DOI: | 10.1016/j.phytochem.2024.114009 |
| Abstrakt: | Seven previously undescribed preurianin-type limonoids, namely paraxylines A-G, and three known analogs were isolated from stem bark of Dysoxylum parasiticum. The structures, including absolute configurations, were established through spectroscopic analyses, quantum chemical calculations using the density functional theory method, as well as the DP4+ algorithm. Paraxylines A-G were identified as the first preurianin-type with full substitution at C, D-rings, leading to the highly oxygenated seco-limonoids skeleton. The secreted alkaline phosphate assay against an engineered human and murine TLR4 of HEK-Blue cells was performed to evaluate the immune regulating effects. Among them, paraxyline B was found to be a remarkable TLR4 agonist whereas two analogs (toonapubesins A and B) were found to antagonise lipopolysaccharide stimulation of the TLR4 pathway. Paraxylines A and C-E acted either as agonists or antagonists depending on the origin of the TLR4 receptor (human or mouse). The effect of these selected compounds on the expression of pro-inflammatory cytokines TNF-α, IL-1α, IL-1β, and IL-6 of the NF-κB signaling pathway were examined in macrophage cell lines, revealing dose-dependent effects. Additionally, paraxylines A, C, D, and G also presented modest cytotoxic activity against MCF-7 and HeLa cell lines with IC Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
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