2. Academic Validation
  3. Antimalarial activity of abietane ferruginol analogues possessing a phthalimide group

Antimalarial activity of abietane ferruginol analogues possessing a phthalimide group

  • Bioorg Med Chem Lett. 2014 Nov 15;24(22):5234-7. doi: 10.1016/j.bmcl.2014.09.061.
Miguel A González 1,  Julie Clark 2,  Michele Connelly 2,  Fatima Rivas 3
Affiliations

Affiliations

  • 1 Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Valencia, Spain. Electronic address: [email protected].
  • 2 Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • 3 Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: [email protected].
PMID: 25316317 DOI: 10.1016/j.bmcl.2014.09.061
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.

Keywords

Abietane; Antimalarial; Dehydroabietylamine; Diterpene; Ferruginol.

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