title: Evaluation of Jatropha isabelli natural products and their synthetic analogs as potential antimalarial therapeutic agents.
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.
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Hadi
authors.forename: Megan
authors.initials: M
authors.lastname: Hotard
authors.forename: Taotao
authors.initials: T
authors.lastname: Ling
authors.forename: Yandira G
authors.initials: YG
authors.lastname: Salinas
authors.forename: Gustavo
authors.initials: G
authors.lastname: Palacios
authors.forename: Michele
authors.initials: M
authors.lastname: Connelly
authors.forename: Fatima
authors.initials: F
authors.lastname: Rivas
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D031286:Jatropha / Q000737:chemistry*; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D001688:Biological Products
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