来自 Heterophylla 属的四氢苯并呋喃-6(2H)-酮新木脂素：它们对血小板激活因子（PAF）的拮抗活性和对 PAF 受体结合模式的计算机模拟研究。

Tetrahydrobenzofuran-6(2 H)-one Neolignans from Ocotea heterochroma: Their Platelet Activating Factor (PAF) Antagonistic Activity and in Silico Insights into the PAF Receptor Binding Mode.

机构信息

Laboratorio de Investigación en Productos Naturales Vegetales, Departamento de Química , Universidad Nacional de Colombia, Ciudad Universitaria , 111321 , Bogotá D.C. , Colombia.

Laboratorio de Química Bioorgánica, Departamento de Química, Facultad de Ciencias Básicas y Aplicadas , Universidad Militar Nueva Granada , 250247 , Cajicá , Colombia.

出版信息

J Nat Prod. 2018 Sep 28;81(9):1968-1975. doi: 10.1021/acs.jnatprod.8b00189. Epub 2018 Sep 6.

DOI:10.1021/acs.jnatprod.8b00189

PMID:30188730

Abstract

Three new tetrahydrobenzofuran-6(2 H)-one-type neolignans, heterochromins A-C (1-3), along with a bicyclo[3.2.1]octane neolignan, cinerin C (4), were isolated from an ethanol extract from the leaves of Ocotea heterochroma, a native plant growing in the Colombo-Ecuadorian region of the Andes. The chemical structures of 1-3 were elucidated by spectroscopic methods. The platelet activating factor (PAF) antagonistic activity was tested in vitro for these compounds. Additionally, their binding mode to the PAF receptor was studied by molecular docking and molecular dynamics simulations in order to rationalize such activity. Heterochromin A (1) was found to be a potent PAF antagonist with a favorable molecular profile for interacting with the PAF receptor binding site.

摘要

从生长在安第斯山脉科罗摩-厄瓜多尔地区的本土植物 Heteropyxis heterochroma 的叶子的乙醇提取物中分离到三种新的四氢苯并呋喃-6(2H)-酮型新木脂素，即异色菌素 A-C（1-3），以及一种双环[3.2.1]辛烷新木脂素，即 cinerin C（4）。通过光谱方法阐明了 1-3 的化学结构。测试了这些化合物在体外对血小板激活因子（PAF）的拮抗活性。此外，通过分子对接和分子动力学模拟研究了它们与 PAF 受体的结合模式，以合理解释这种活性。发现异色菌素 A（1）是一种有效的 PAF 拮抗剂，具有与 PAF 受体结合位点相互作用的有利分子特征。