title: Synthesis, antimalarial activity, and structure-activity relationship of 7-(2-phenoxyethoxy)-4(1H)-quinolones.
abstract: ICI 56,780 (5) displayed causal prophylactic and blood schizonticidal activity (ED50=0.05 mg/kg) in rodent malaria models but produced rapid acquisition of parasitological resistance in P. berghei infected mice. Herein we describe the synthesis of analogues of 5 with EC50 as low as 0.15 nM against multidrug resistant P. falciparum. Optimal activity with low cross-resistance indexes (RI) to atovaquone was achieved by introducing ortho-substituted aryl moieties at the 3-position of the 7-(2-phenoxyethoxy)-4(1H)-quinolone core.
authors: Department of Chemistry, University of South Florida, CHE 205, 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
authors: R Matthew
authors: RM
authors: Cross
authors: Niranjan K
authors: NK
authors: Namelikonda
authors: Tina S
authors: TS
authors: Mutka
authors: Lisa
authors: L
authors: Luong
authors: Dennis E
authors: DE
authors: Kyle
authors: Roman
authors: R
authors: Manetsch
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053626:Atovaquone / Q000494:pharmacology; D002460:Cell Line; D004351:Drug Resistance; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D015363:Quinolones; D053626:Atovaquone