Antimalarial activity of WR 243251, a dihydroacridinedione

J. Berman, L. Brown, R. Miller, S. L. Andersen, P. McGreevy, B. G. Schuster, W. Ellis, Arba L Ager, R. Rossan

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1753-1756
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume38
Issue number8
StatePublished - 1994
Externally publishedYes

Fingerprint

Chloroquine
Antimalarials
Haplorhini
Parasites
Mefloquine
Plasmodium berghei
Pyrimethamine
Plasmodium falciparum
Oral Administration
Body Weight
WR 243251
Pharmaceutical Preparations
In Vitro Techniques

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Berman, J., Brown, L., Miller, R., Andersen, S. L., McGreevy, P., Schuster, B. G., ... Rossan, R. (1994). Antimalarial activity of WR 243251, a dihydroacridinedione. Antimicrobial Agents and Chemotherapy, 38(8), 1753-1756.

Antimalarial activity of WR 243251, a dihydroacridinedione. / Berman, J.; Brown, L.; Miller, R.; Andersen, S. L.; McGreevy, P.; Schuster, B. G.; Ellis, W.; Ager, Arba L; Rossan, R.

In: Antimicrobial Agents and Chemotherapy, Vol. 38, No. 8, 1994, p. 1753-1756.

Research output: Contribution to journalArticle

Berman, J, Brown, L, Miller, R, Andersen, SL, McGreevy, P, Schuster, BG, Ellis, W, Ager, AL & Rossan, R 1994, 'Antimalarial activity of WR 243251, a dihydroacridinedione', Antimicrobial Agents and Chemotherapy, vol. 38, no. 8, pp. 1753-1756.
Berman J, Brown L, Miller R, Andersen SL, McGreevy P, Schuster BG et al. Antimalarial activity of WR 243251, a dihydroacridinedione. Antimicrobial Agents and Chemotherapy. 1994;38(8):1753-1756.
Berman, J. ; Brown, L. ; Miller, R. ; Andersen, S. L. ; McGreevy, P. ; Schuster, B. G. ; Ellis, W. ; Ager, Arba L ; Rossan, R. / Antimalarial activity of WR 243251, a dihydroacridinedione. In: Antimicrobial Agents and Chemotherapy. 1994 ; Vol. 38, No. 8. pp. 1753-1756.
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