Biomaterial Database

New, antimalarial, tricyclic 1,2,4-trioxanes: evaluations in mice and monkeys. 1994

G H Posner, and C H Oh, and H K Webster, and A L Ager, and R N Rossan

Department of Chemistry, Johns Hopkins University, Baltimore, Maryland.

We have concluded initial preclinical studies with synthetic trioxanes numbered 3-9 and have compared them with artemisinin (numbered 1) using CD-1 mice infected with Plasmodium berghei. Based on their antimalarial effectiveness in mice, two of these synthetic trioxanes were selected for evaluation in Aotus monkeys infected with multidrug-resistant (MDR) P. falciparum. Trioxane numbered 8 (12 and 48 mg/kg), trioxane numbered 9 (12 and 48 mg/kg) and arteether (numbered 2, 48 mg/kg) were administered intramuscularly in three 12-hr doses to A. lemurinus lemurinus (Panamanian owl monkeys) infected with the Vietnam Smith/RE strain of P. falciparum and monitored for parasitemia. Trioxane numbered 8 at 12 mg/kg cleared parasitemia in two monkeys, but recrudescence occurred in one animal. Treatment of the recrudescent infection with 48 mg/kg was curative. Infections in two monkeys treated initially with 48 mg/kg were cured (six-month follow-up). Trioxane numbered 9 produced a similar outcome: 12 mg/kg suppressed parasitemia in two monkeys but was not curative; however, 48 mg/kg cured infections in all four monkeys treated. These preliminary observations show synthetic trioxanes numbered 8 and 9 to be as effective as arteether (numbered 2) against MDR in P. falciparum in the Aotus monkey.

UI	MeSH Term	Description	Entries
D008288	Malaria	A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.	Marsh Fever,Plasmodium Infections,Remittent Fever,Infections, Plasmodium,Paludism,Fever, Marsh,Fever, Remittent,Infection, Plasmodium,Plasmodium Infection
D010962	Plasmodium berghei	A protozoan parasite of rodents transmitted by the mosquito Anopheles dureni.	Plasmodium bergheus,berghei, Plasmodium
D001952	Bridged-Ring Compounds	Cyclic hydrocarbons that contain multiple rings which share one or more bridgehead connections.	Bridged Compounds,Bridged Ring Compounds
D006571	Heterocyclic Compounds	Cyclic compounds that include atoms other than carbon in their ring structure.	Heterocyclic Compound,Compound, Heterocyclic,Compounds, Heterocyclic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000962	Antimalarials	Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)	Anti-Malarial,Antimalarial,Antimalarial Agent,Antimalarial Drug,Anti-Malarials,Antimalarial Agents,Antimalarial Drugs,Agent, Antimalarial,Agents, Antimalarial,Anti Malarial,Anti Malarials,Drug, Antimalarial,Drugs, Antimalarial
D001029	Aotus trivirgatus	A species in the family AOTIDAE, inhabiting the forested regions of Central and South America (from Panama to the Amazon). Vocalizations occur primarily at night when they are active, thus they are also known as Northern night monkeys.	Humboldt's Night Monkey,Monkey, Northern Night,Night Monkey, Northern,Humboldt Night Monkey,Humboldts Night Monkey,Monkey, Humboldt's Night,Night Monkey, Humboldt's,Northern Night Monkey,Northern Night Monkeys
D012717	Sesquiterpenes	Fifteen-carbon compounds formed from three isoprenoid units with general formula C15H24.	Farnesanes,Farnesene,Farnesenes,Sesquiterpene,Sesquiterpene Derivatives,Sesquiterpenoid,Sesquiterpenoids,Derivatives, Sesquiterpene
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D016778	Malaria, Falciparum	Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.	Plasmodium falciparum Malaria,Malaria, Plasmodium falciparum