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Elsevier, Bioorganic and Medicinal Chemistry Letters, 22(24), p. 5234-5237

DOI: 10.1016/j.bmcl.2014.09.061

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Antimalarial Activity of Abietane Ferruginol Analogues Possessing a Phthalimide Group

Journal article published in 2014 by Miguel A. González ORCID, Julie Clark, Michele Connelly, Fatima Rivas
This paper is available in a repository.
This paper is available in a repository.

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Abstract

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.