title: Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria.
abstract: Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis (DOS) led to the initial hit. Structure-activity relationships guided the synthesis of compounds having improved potency and water solubility, yielding a subnanomolar inhibitor of parasite asexual blood-stage growth. Optimized compound 27 has an excellent off-target activity profile in erythrocyte lysis and HepG2 assays and is stable in human plasma. This compound is available via the molecular libraries probe production centers network (MLPCN) and is designated ML238.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Heidebrecht
authors.forename: Carol
authors.initials: C
authors.lastname: Mulrooney
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Austin
authors.forename: Robert H
authors.initials: RH
authors.lastname: Barker
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Beaudoin
authors.forename: Ken Chih-Chien
authors.initials: KC
authors.lastname: Cheng
authors.forename: Eamon
authors.initials: E
authors.lastname: Comer
authors.forename: Sivaraman
authors.initials: S
authors.lastname: Dandapani
authors.forename: Justin
authors.initials: J
authors.lastname: Dick
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Duvall
authors.forename: Eric H
authors.initials: EH
authors.lastname: Ekland
authors.forename: David A
authors.initials: DA
authors.lastname: Fidock
authors.forename: Mark E
authors.initials: ME
authors.lastname: Fitzgerald
authors.forename: Michael
authors.initials: M
authors.lastname: Foley
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Guha
authors.forename: Paul
authors.initials: P
authors.lastname: Hinkson
authors.forename: Martin
authors.initials: M
authors.lastname: Kramer
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Lukens
authors.forename: Daniela
authors.initials: D
authors.lastname: Masi
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Marcaurelle
authors.forename: Xin-Zhuan
authors.initials: XZ
authors.lastname: Su
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Thomas
authors.forename: Michel
authors.initials: M
authors.lastname: Weïwer
authors.forename: Roger C
authors.initials: RC
authors.lastname: Wiegand
authors.forename: Dyann
authors.initials: D
authors.lastname: Wirth
authors.forename: Menghang
authors.initials: M
authors.lastname: Xia
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Jinghua
authors.initials: J
authors.lastname: Zhao
authors.forename: Michelle
authors.initials: M
authors.lastname: Palmer
authors.forename: Benito
authors.initials: B
authors.lastname: Munoz
authors.forename: Stuart
authors.initials: S
authors.lastname: Schreiber