guianensis的油具有杀利什曼活性,它的活动与柠檬苦素有关,但是脂肪酸是这种油的主要成分。本研究评估了物理化学,药代动力学,以及已经在该物种中鉴定的柠檬苦素和脂肪酸的毒性谱。基于这些结果,2limonoids(甲基angosinate,选择6-OH-甲基angosinate)和2种脂肪酸(花生酸;肉豆蔻酸)来预测可能的靶标和分子对接。这项研究包括:Gedunin,6α-乙酰氧化杜宁,甲基angosenlato,7-脱乙酰氧基-7-氧代杜宁,安迪罗宾,6-羟基-angolensate甲酯,17β-羟基氮杂二酮,1,2-二氢-3β-羟基-7-脱乙酰氧基-7-氧代杜宁,木门素k,11β-羟基氧化杜宁,6α,11-11β-二乙酰氧化乙宁,油酸,棕榈酸,硬脂酸,花生酸,肉豆蔻酸,棕榈油酸,亚油酸,亚麻酸,和BeenicAcid.关于物理化学方面,脂肪酸违反了LogP,只有limonoid11违反了Lipinski的规则。常见的药代动力学方面是所有分子在肠道中都很好地吸收并抑制CYP。所有化合物在某些模型中都显示出毒性,脂肪酸是诱变和致癌的,和柠檬苦素至少对大鼠没有诱变和致癌作用。在体内模型中,脂肪酸毒性较小。分子对接对COX-2类固醇(15和16)和缺氧诱导因子1α进行柠檬苦素(3,6),该靶标对于利什曼原虫的细胞内发育至关重要。limonoids3和6似乎有希望作为利什曼杀菌剂,和脂肪酸有望成为伤口治疗者。
The oil of Carapa guianensis showed leishmanicidal activity, with its activity being related to limonoids, but fatty acids are the major constituents of this oil. The present study evaluated the physicochemical, pharmacokinetic, and toxicity profiles of limonoids and fatty acids already identified in the species. Based on these results, 2 limonoids (methyl angosinlate, 6-OH-methyl angosinlate) and 2 fatty acids (arachidic acid; myristic acid) were selected for the prediction of possible targets and molecular docking. Included in this study were: Gedunin, 6α-acetoxygedunin, Methyl angosenlato, 7-deacetoxy-7-oxogedunin, Andirobin, 6-hydroxy-angolensate methyl, 17β-hydroxyazadiradione, 1,2-dihydro-3β-hydroxy-7-deacetoxy-7-oxogedunin, xyllocensin k, 11beta-Hydroxygedunin, 6α,11-11β-diacetoxygedunin, Oleic Acid, Palmitic Acid, Stearic Acid, Arachidic Acid, Myristic Acid, Palmitoleic Acid, Linoleic Acid, Linolenic Acid, and Beenic Acid. Regarding physicochemical aspects, fatty acids violated LogP, and only limonoid 11 violated Lipinski\'s rule. A common pharmacokinetic aspect was that all molecules were well absorbed in the intestine and inhibited CYP. All compounds showed toxicity in some model, with fatty acids being mutagenic and carcinogenic, and limonoids not being mutagenic and carcinogenic at least for rats. In in vivo models, fatty acids were less toxic. Molecular dockings were performed on COX-2 steroids (15 and 16) and hypoxia-inducible factor 1 alpha for limonoids (3,6), with this target being essential for the intracellular development of leishmania. Limonoids 3 and 6 appear to be promising as leishmanicidal agents, and fatty acids are promising as wound healers.