Antimalarial activity of WR 243251, a Dihydroacridinedione
| Autor: | Arba L. Ager, L Brown, Brian G. Schuster, P McGreevy, William Y. Ellis, Susan L. Andersen, Richard N. Rossan, Judith Berman, Robert E. Miller |
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| Rok vydání: | 1994 |
| Předmět: |
Plasmodium falciparum
Drug Resistance Drug resistance Biology Pharmacology Antimalarials Mice In vivo Chloroquine parasitic diseases medicine Animals Pharmacology (medical) Plasmodium berghei Antimalarial Agent Malaria Falciparum Strain (chemistry) Biological activity biology.organism_classification Infectious Diseases Aotus trivirgatus Acridines Research Article medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 38:1753-1756 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.38.8.1753 |
| Popis: | WR 243251 is a dihydroacridinedione that was evaluated for antimalarial blood schizonticidal activity in vitro and in vivo. The in vitro doses calculated to kill 50% of organisms were 11 nM for a chloroquine-susceptible, mefloquine-resistant standard strain and 25 nM for a chloroquine- and pyrimethamine-resistant standard strain. The total dose needed to cure 100% of mice infected with a drug-susceptible strain of Plasmodium berghei was 12 to 20 mg/kg of body weight for both oral and subcutaneous administration. The regimen needed to cure 100% of Aotus monkeys infected with Plasmodium falciparum was 8 mg/kg/day for 3 days (chloroquine-susceptible strain) and 16 mg/kg/day for 3 days (chloroquine-resistant strain). The 100% curative doses for Aotus monkeys did not increase for parasites previously exposed to subcurative doses. The absolute value of the curative doses of WR 243251 was comparable to or lower than the values for clinical antimalarial agents. The high absolute activity, comparability of activities against susceptible and resistant parasites, and inability to induce resistance by exposure to subcurative doses suggest that WR 243251 has strong potential as a blood schizonticidal agent. |
| Databáze: | OpenAIRE |
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