结构多样化的triterpene-26-oic酸作为脆弱针叶树的潜在双重ACL和ACC1抑制剂
Ze-Yu Zhao1,2, Ying-Peng Tong2, Wei Jiang1,3
1Department of Natural Medicine, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China.
Journal of natural products
|June 8, 2023
概括
研究人员从Keteleeria fortunei发现了17种三类植物,其中包括9种新植物. 一些化合物抑制糖脂代谢中的关键酶,为新的ACL和ACC1疗法提供了潜力.
科学领域:
- 植物化学 植物化学
- 自然产品 化学 化学
- 药用化学 医学化学
背景情况:
- 一种易受伤害的针叶树 Keteleeria fortunei 是各种化学化合物的来源.
- 三类是具有各种生物活动的自然产品的一类.
- 像腺三酸盐 (ATP) - 酸酶 (ACL) 和乙烯基-CoA碳酸酶1 (ACC1) 这样的酶在糖脂代谢中至关重要.
研究的目的:
- 从Keteleeria fortunei中分离和表征三类植物.
- 研究这些化合物对ACL和ACC1.1的抑制作用.
- 探索这些天然产品作为代谢疾病治疗剂的潜力.
主要方法:
- 使用90%的MeOH提取物进行了植物化学研究.
- 通过广泛的光谱方法 (2D NMR) 和计算计算 (NMR/ECD) 阐明结构.
- 使用修改的莫舍尔法和单晶X射线衍射来确定绝对配置.
- 对ACL和ACC1.1进行酶抑制测定.
- 分子对接研究,以检查酶-连接体相互作用.
主要成果:
- 隔离和表征17种三类,包括9种新型福特酸 (1-9).
- 独特的三类骨的鉴定: 9βH-拉诺斯坦,17,14-弗里多-拉诺斯坦和17,13-弗里多-环亚坦.
- 福特酸B (2),G (7),I (9),异构酸 (12),和3α,27-二基环-24E-en-26-oic酸 (14) 显示出ACL和ACC1.1的双抑制.
- 抑制的IC50值在ACL的5.711.4微米和ACC1.5的7.510.5微米之间.
- 分子对接支持生物活性三和目标酶之间的相互作用.
结论:
- 这项研究扩大了来自Keteleeria fortunei的三类的化学多样性.
- 某些孤立的三烯酸对ACL和ACC1.1具有显著的抑制活性.
- 这些发现强调了保护植物多样性的重要性,以发现新的药物道.
- 已识别的化合物代表了与失调的糖脂代谢相关的疾病的潜在治疗候选者.
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