Synthesis and antimalarial property of orally active phenoxazinium salts.
Phenoxazinium salts were found to display good antimalarial efficacy in vivo against Plasmodium berghei. Several compounds provided 100% parasitemia clearance at a dose of 20-30 mg kg-1x4 days (ip) and good survival effects without obvious acute toxicity. They also showed excellent potency by oral administration. A preliminary pharmacokinetic study revealed that the oral availability of 1a was excellent.
Takasu
Kiyosei
K
Shimogama
Tsubasa
T
Satoh
Chie
C
Kaiser
Marcel
M
Brun
Reto
R
Ihara
Masataka
M
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004351:Drug Resistance; D007928:Lethal Dose 50; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000962:Antimalarials; D010078:Oxazines; D000644:Quaternary Ammonium Compounds