Evaluation of Jatropha isabelli natural products and their synthetic analogs as potential antimalarial therapeutic agents

  • Eur J Med Chem. 2013 Jul:65:376-80. doi: 10.1016/j.ejmech.2013.04.030.
Victor Hadi  1 ,  Megan Hotard ,  Taotao Ling ,  Yandira G Salinas ,  Gustavo Palacios ,  Michele Connelly ,  Fatima Rivas
Affiliations
  • 1. Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA.
PMID: 23747806 DOI: 10.1016/j.ejmech.2013.04.030
Abstract

Protozoal diseases such as malaria are a leading world health concern. We screened a library of fractionated natural products to identify new potential therapeutic leads and discovered that jatrophone (a product of Jatropha isabelli) exerts significant activity against Plasmodium falciparum strains 3D7 and K1. A focused jatrophone-scaffold library was synthesized to evaluate jatrophone's mode of action and identify more selective analogs. Compounds 25 and 32 of this natural product-inspired compound library exhibited micromolar EC50 values against strains 3D7 and K1, thus providing a new antimalarial molecular scaffold. Our report describes an efficient derivatization approach used to evaluate the structure-activity relationship of jatrophone analogs in search of potential new antimalarial agents.

Keywords
1-butyl-3-methylimidazolium tetrafluoroborate; Antimalarial agents; Conjugated additions; Jatropha isabelli; Jatrophone; N-bromosuccinimide; NBS; PAMPA; Plasmodium falciparum; [bmim][BF(4)]; mCPBA; meta-chloroperoxybenzoic acid; parallel artificial membrane permeability assay.