title: Synthesis and evaluation of naphthyridine compounds as antimalarial agents.
abstract: Primaquine is the drug of choice for the radical cure of Plasmodium vivax malaria, but possesses serious side effects. In this study novel primaquine analogues were designed and synthesized. Lower toxicity was achieved by reducing or eliminating the tendency of forming chemically reactive and toxic intermediates and metabolites. In vitro and in vivo studies found that synthesized compounds were less toxic than the parent compound primaquine, while preserving the desired antimalarial activity. Some of these compounds possess a therapeutic index over 10 times superior to that of the commonly used antimalarial drug chloroquine. These compounds, as well as the underlying design rationale, may find usefulness in the discovery and development of new antimalarial drugs.
authors: Radix Pharmaceuticals Inc., 880 College Parkway, Rockville, MD 20850, USA. shuren.zhu@gmail.com
authors: Shuren
authors: S
authors: Zhu
authors: Quan
authors: Q
authors: Zhang
authors: Chandrashekar
authors: C
authors: Gudise
authors: Li
authors: L
authors: Meng
authors: Lai
authors: L
authors: Wei
authors: Erika
authors: E
authors: Smith
authors: Yuliang
authors: Y
authors: Kong
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy*; D015394:Molecular Structure; D051189:Murinae; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D021261:Parasitic Sensitivity Tests; D010961:Plasmodium / Q000187:drug effects; D011319:Primaquine / Q000031:analogs & derivatives* / Q000737:chemistry; D023382:Toxicity Tests, Acute
chemical_list: D000962:Antimalarials; D009287:Naphthyridines; D011319:Primaquine