title: Simplified Reversed Chloroquines To Overcome Malaria Resistance to Quinoline-Based Drugs.
abstract: Building on our earlier work of attaching a chemosensitizer (reversal agent) to a known drug pharmacophore, we have now expanded the structure-activity relationship study to include simplified versions of the chemosensitizer. The change from two aromatic rings in this head group to a single ring does not appear to detrimentally affect the antimalarial activity of the compounds. Data fromin vitroheme binding andβ-hematin inhibition assays suggest that the single aromatic RCQ compounds retain activities againstPlasmodium falciparumsimilar to those of CQ, although other mechanisms of action may be relevant to their activities.
authors.affiliation: Department of Chemistry, Portland State University, Portland, Oregon, USA.
authors.forename: Bornface
authors.initials: B
authors.lastname: Gunsaru
authors.affiliation: Department of Chemistry, Portland State University, Portland, Oregon, USA.|DesignMedix, Inc., Portland, Oregon, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Burgess
authors.affiliation: DesignMedix, Inc., Portland, Oregon, USA.
authors.forename: Westin
authors.initials: W
authors.lastname: Morrill
authors.affiliation: Department of Chemistry, Portland State University, Portland, Oregon, USA.|Portland Veterans Affairs Medical Center, Portland, Oregon, USA.|DesignMedix, Inc., Portland, Oregon, USA.
authors.forename: Jane X
authors.initials: JX
authors.lastname: Kelly
authors.affiliation: Department of Chemistry, Portland State University, Portland, Oregon, USA.|DesignMedix, Inc., Portland, Oregon, USA.
authors.forename: Shawheen
authors.initials: S
authors.lastname: Shomloo
authors.affiliation: Portland Veterans Affairs Medical Center, Portland, Oregon, USA.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Smilkstein
authors.affiliation: Department of Chemistry, Portland State University, Portland, Oregon, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Liebman
authors.affiliation: Department of Chemistry, Portland State University, Portland, Oregon, USA peytond@pdx.edu.|DesignMedix, Inc., Portland, Oregon, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Peyton
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D005260:Female; D006418:Heme / Q000378:metabolism; D006420:Hemeproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016778:Malaria, Falciparum / Q000188:drug therapy*; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects*; D010967:Plasmodium yoelii / Q000187:drug effects*; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D006420:Hemeproteins; C020753:hemozoin; D006418:Heme; D002738:Chloroquine
keywords: Plasmodium falciparum; accumulation; antimalarial; chloroquine; drug development; drug discovery; drug resistance; hematin; hemozoin; malaria; structure-activity relationship