title: Identification of Compounds with Efficacy against Malaria Parasites from Common North American Plants.
abstract: Some of the most valuable antimalarial compounds, including quinine and artemisinin, originated from plants. While these drugs have served important roles over many years for the treatment of malaria, drug resistance has become a widespread problem. Therefore, a critical need exists to identify new compounds that have efficacy against drug-resistant malaria strains. In the current study, extracts prepared from plants readily obtained from local sources were screened for activity against Plasmodium falciparum. Bioassay-guided fractionation was used to identify 18 compounds from five plant species. These compounds included eight lupane triterpenes (1-8), four kaempferol 3-O-rhamnosides (10-13), four kaempferol 3-O-glucosides (14-17), and the known compounds amentoflavone and knipholone. These compounds were tested for their efficacy against multi-drug-resistant malaria parasites and counterscreened against HeLa cells to measure their antimalarial selectivity. Most notably, one of the new lupane triterpenes (3) isolated from the supercritical extract of Buxus sempervirens, the common boxwood, showed activity against both drug-sensitive and -resistant malaria strains at a concentration that was 75-fold more selective for the drug-resistant malaria parasites as compared to HeLa cells. This study demonstrates that new antimalarial compounds with efficacy against drug-resistant strains can be identified from native and introduced plant species in the United States, which traditionally have received scant investigation compared to more heavily explored tropical and semitropical botanical resources from around the world.
authors.forename: Shengxin
authors.initials: S
authors.lastname: Cai
authors.forename: April L
authors.initials: AL
authors.lastname: Risinger
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute , San Antonio, Texas 78227, United States.
authors.forename: Shalini
authors.initials: S
authors.lastname: Nair
authors.forename: Jiangnan
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute , San Antonio, Texas 78227, United States.
authors.forename: Timothy J C
authors.initials: TJ
authors.lastname: Anderson
authors.forename: Lin
authors.initials: L
authors.lastname: Du
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Powell
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mooberry
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cichewicz
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology; D004351:Drug Resistance / Q000187:drug effects; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects*; D011803:Quinine / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014481:United States; D053978:Pentacyclic Triterpenes; D000094062:Betulinic Acid
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D006027:Glycosides; D011803:Quinine; D014315:Triterpenes; C480546:lupane; D053978:Pentacyclic Triterpenes; C002503:betulin; D000094062:Betulinic Acid; C031327:artemisinin