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从……叶片中分离得到的高选择性烷基香豆素和二萜类化合物:寻找针对……的新型活性化合物

Highly selective alkylcoumarates and diterpenoids isolated from leaves of : a search for new hit compounds against .

作者信息

Peres Nathalia, Silva Matheus L, Ueno Anderson K, Antar Guilherme M, Levatti Erica V C, Tempone Andre G, Lago João Henrique G

机构信息

Center for Natural and Human Sciences, Federal University of ABC, Santo André, Brazil.

Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, São Paulo, Brazil.

出版信息

Nat Prod Res. 2024 Mar 27:1-7. doi: 10.1080/14786419.2024.2335362.

Abstract

In the present work, the hexane extract of aerial parts of Kunth. was subjected to chromatographic fractionation to afford two alkyl phenylpropanoids: -docosyl (-coumarate () and -tetracosyl -coumarate () as well as five diterpenes: kaurenoic acid (), grandifloric acid (), 15β-senecioyl-oxy--kaur-16-en-19-oic acid (), and 15-oxo--kaurenoic acid (). Using an assay with macrophages infected with , compounds and demonstrated high potency against intracellular amastigotes, with EC values of 7.5 and 6.9 µM, respectively. Compound revealed a moderate potency against , with an EC of 25.6 µM, and compounds showed no effectiveness. Additionally, compounds compounds presented no toxicity for mammalian cells to the highest tested concentration of 200 µM. Based on potency and the selectivity indexes of , and , these compounds could be future candidates for optimisation studies for the design of prototypes against Chagas disease.

摘要

在本研究中,对Kunth地上部分的己烷提取物进行色谱分离,得到两种烷基苯丙烷类化合物:-二十二烷基(-香豆酸()和-二十四烷基-香豆酸()以及五种二萜类化合物:贝壳杉烯酸()、大花酸()、15β-千里光酰氧基--贝壳杉-16-烯-19-酸()和15-氧代--贝壳杉烯酸()。通过对感染的巨噬细胞进行检测,化合物和对细胞内无鞭毛体显示出高效力,其EC值分别为7.5和6.9 μM。化合物对显示出中等效力,EC为25.6 μM,而化合物则无效果。此外,化合物在最高测试浓度200 μM时对哺乳动物细胞无毒性。基于、和的效力及选择性指数,这些化合物可能是未来针对恰加斯病设计原型进行优化研究的候选物。

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