title: Structure-activity relationships amongst 4-position quinoline methanol antimalarials that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum.
abstract: Utilizing mefloquine as a scaffold, a next generation quinoline methanol (NGQM) library was constructed to identify early lead compounds that possess biological properties consistent with the target product profile for malaria chemoprophylaxis while reducing permeability across the blood-brain barrier. The library of 200 analogs resulted in compounds that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum. Herein we report selected chemotypes and the emerging structure-activity relationship for this library of quinoline methanols.
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, USA. erin.milner@us.army.mil
authors.forename: Erin
authors.initials: E
authors.lastname: Milner
authors.forename: William
authors.initials: W
authors.lastname: McCalmont
authors.forename: Jayendra
authors.initials: J
authors.lastname: Bhonsle
authors.forename: Diana
authors.initials: D
authors.lastname: Caridha
authors.forename: Dustin
authors.initials: D
authors.lastname: Carroll
authors.forename: Sean
authors.initials: S
authors.lastname: Gardner
authors.forename: Lucia
authors.initials: L
authors.lastname: Gerena
authors.forename: Montip
authors.initials: M
authors.lastname: Gettayacamin
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lanteri
authors.forename: Thulan
authors.initials: T
authors.lastname: Luong
authors.forename: Victor
authors.initials: V
authors.lastname: Melendez
authors.forename: Jay
authors.initials: J
authors.lastname: Moon
authors.forename: Norma
authors.initials: N
authors.lastname: Roncal
authors.forename: Jason
authors.initials: J
authors.lastname: Sousa
authors.forename: Anchalee
authors.initials: A
authors.lastname: Tungtaeng
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Dow
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D025141:Drug Resistance, Fungal; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D011804:Quinolines; D054852:Small Molecule Libraries