Structure-activity relationships amongst 4-position quinoline methanol antimalarials that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum.
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.
Milner
Erin
E
Walter Reed Army Institute of Research, Silver Spring, MD, USA. erin.milner@us.army.mil
McCalmont
William
W
Bhonsle
Jayendra
J
Caridha
Diana
D
Carroll
Dustin
D
Gardner
Sean
S
Gerena
Lucia
L
Gettayacamin
Montip
M
Lanteri
Charlotte
C
Luong
Thulan
T
Melendez
Victor
V
Moon
Jay
J
Roncal
Norma
N
Sousa
Jason
J
Tungtaeng
Anchalee
A
Wipf
Peter
P
Dow
Geoffrey
G
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
D000962:Antimalarials; D011804:Quinolines; D054852:Small Molecule Libraries