Antimalarial activity of abietane ferruginol analogues possessing a phthalimide group

被引：47

作者：

Gonzalez, Miguel A. ^{[1
]}

Clark, Julie ^{[2
]}

Connelly, Michele ^{[2
]}

Rivas, Fatima ^{[2
]}

机构：

[1] Univ Valencia, Dept Quim Organ, E-46100 Burjassot, Spain

[2] St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 22期

关键词：

Antimalarial; Abietane; Diterpene; Ferruginol; Dehydroabietylamine; PLASMODIUM-FALCIPARUM; NATURAL-PRODUCTS; CANCER CELLS; DERIVATIVES; DITERPENES; AGENTS; (+)-DEHYDROABIETYLAMINE; CONSTITUENTS; RING;

D O I：

10.1016/j.bmcl.2014.09.061

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The abietane-type diterpenoid (+)-ferruginol, a bioactive compound isolated from New Zealand's Miro tree (Podocarpus ferruginea), displays relevant pharmacological properties, including antimicrobial, cardioprotective, anti-oxidative, anti-plasmodial, leishmanicidal, anti-ulcerogenic, anti-inflammatory and anticancer. Herein, we demonstrate that ferruginol (1) and some phthalimide containing analogues 2-12 have potential antimalarial activity. The compounds were evaluated against malaria strains 3D7 and K1, and cytotoxicity was measured against a mammalian cell line panel. A promising lead, compound 3, showed potent activity with an EC50 = 86 nM (3D7 strain), 201 nM (K1 strain) and low cytotoxicity in mammalian cells (SI > 290). Some structure-activity relationships have been identified for the antimalarial activity in these abietane analogues. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：5234 / 5237

页数：4

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