title: Discovery of new antimalarial chemotypes through chemical methodology and library development.
abstract: In an effort to expand the stereochemical and structural complexity of chemical libraries used in drug discovery, the Center for Chemical Methodology and Library Development at Boston University has established an infrastructure to translate methodologies accessing diverse chemotypes into arrayed libraries for biological evaluation. In a collaborative effort, the NIH Chemical Genomics Center determined IC(50)'s for Plasmodium falciparum viability for each of 2,070 members of the CMLD-BU compound collection using quantitative high-throughput screening across five parasite lines of distinct geographic origin. Three compound classes displaying either differential or comprehensive antimalarial activity across the lines were identified, and the nascent structure activity relationships (SAR) from this experiment used to initiate optimization of these chemotypes for further development.
authors.affiliation: Department of Chemistry and Center for Chemical Methodology and Library Development, Boston University, 590 Commonwealth Avenue, Boston, MA 02215.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Brown
authors.forename: Ken
authors.initials: K
authors.lastname: Chih-Chien Cheng
authors.forename: Wan-Guo
authors.initials: WG
authors.lastname: Wei
authors.forename: Pingwei
authors.initials: P
authors.lastname: Yuan
authors.forename: Peng
authors.initials: P
authors.lastname: Dai
authors.forename: Richard
authors.initials: R
authors.lastname: Trilles
authors.forename: Feng
authors.initials: F
authors.lastname: Ni
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Ryan
authors.initials: R
authors.lastname: MacArthur
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Guha
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Johnson
authors.forename: Xin-zhuan
authors.initials: XZ
authors.lastname: Su
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Dominguez
authors.forename: John K
authors.initials: JK
authors.lastname: Snyder
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Beeler
authors.forename: Scott E
authors.initials: SE
authors.lastname: Schaus
authors.forename: James
authors.initials: J
authors.lastname: Inglese
authors.forename: John A
authors.initials: JA
authors.lastname: Porco
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000254:growth & development*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials