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Structure-Activity Relationships of Pentacyclic Triterpenoids as Inhibitors of Cyclooxygenase and Lipoxygenase Enzymes.
Journal of Natural Products ( IF 3.3 ) Pub Date : 2019-11-27 , DOI: 10.1021/acs.jnatprod.9b00538 Nhu Ngoc Quynh Vo 1 , Yuhta Nomura 1, 2 , Toshiya Muranaka 1 , Ery Odette Fukushima 1, 3, 4
Journal of Natural Products ( IF 3.3 ) Pub Date : 2019-11-27 , DOI: 10.1021/acs.jnatprod.9b00538 Nhu Ngoc Quynh Vo 1 , Yuhta Nomura 1, 2 , Toshiya Muranaka 1 , Ery Odette Fukushima 1, 3, 4
Affiliation
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Pentacyclic triterpenes may be active agents and provide a rich natural resource of promising compounds for drug development. The inhibitory activities of 29 natural oleanane and ursane pentacyclic triterpenes were evaluated against four major enzymes involved in the inflammatory process: 5-LOX, 15-LOX-2, COX-1, and COX-2. It was found that 3-O-acetyl-β-boswellic acid potently inhibited human 15-LOX-2 (IC50 = 12.2 ± 0.47 μM). Analysis of the structure-activity relationships revealed that the presence of a hydroxy group at position 24 was beneficial in terms of both 5-LOX and COX-1 inhibition. Notably, the introduction of a carboxylic acid group at position 30 was important for dual 5-LOX/COX inhibitory activity; furthermore, its combination with a carbonyl group at C-11 considerably increased 5-LOX inhibition. Also, the presence of an α-hydroxy group at C-2 or a carboxylic acid group at C-23 markedly suppressed the 5-LOX activity. The present findings reveal that the types and configurations of polar moieties at positions C-2, -3, -11, -24, and -30 are important structural aspects of pentacyclic triterpenes for their potential as anti-inflammatory lead compounds.
中文翻译：
五环三萜作为环氧合酶和脂氧合酶抑制剂的结构活性关系。
五环三萜可能是活性剂，并为药物开发提供了有希望的化合物的丰富天然资源。评估了29种天然齐墩果烷和乌苏烷五环三萜对四种参与炎症过程的主要酶的抑制活性：5-LOX，15-LOX-2，COX-1和COX-2。发现3-O-乙酰基-β-乳香酸有效抑制人15-LOX-2（IC50 ＝ 12.2±0.47μM）。结构活性关系的分析表明，就5-LOX和COX-1抑制而言，在24位羟基的存在是有益的。值得注意的是，在30位引入羧基对于双重抑制5-LOX / COX的活性很重要。此外，它与C-11处的羰基结合大大提高了5-LOX抑制作用。还，C-2处的α-羟基或C-23处的羧酸基的存在显着抑制了5-LOX活性。本发现表明，在位置C-2，-3，-11，-24和-30的极性部分的类型和构型是五环三萜作为抗炎先导化合物的潜力的重要结构方面。
更新日期：2019-11-28
中文翻译：
五环三萜作为环氧合酶和脂氧合酶抑制剂的结构活性关系。
五环三萜可能是活性剂，并为药物开发提供了有希望的化合物的丰富天然资源。评估了29种天然齐墩果烷和乌苏烷五环三萜对四种参与炎症过程的主要酶的抑制活性：5-LOX，15-LOX-2，COX-1和COX-2。发现3-O-乙酰基-β-乳香酸有效抑制人15-LOX-2（IC50 ＝ 12.2±0.47μM）。结构活性关系的分析表明，就5-LOX和COX-1抑制而言，在24位羟基的存在是有益的。值得注意的是，在30位引入羧基对于双重抑制5-LOX / COX的活性很重要。此外，它与C-11处的羰基结合大大提高了5-LOX抑制作用。还，C-2处的α-羟基或C-23处的羧酸基的存在显着抑制了5-LOX活性。本发现表明，在位置C-2，-3，-11，-24和-30的极性部分的类型和构型是五环三萜作为抗炎先导化合物的潜力的重要结构方面。
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