Antimalarial Activities of Various 9-Phenanthrenemethanols with Special Attention to WR-122,455 and WR-171,669
- 1 September 1978
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 14 (3), 292-314
- https://doi.org/10.1128/aac.14.3.292
Abstract
Pilot appraisals of the activities of 16 specially selected 9-phenanthrenemethanols against acute infections with Plasmodium falciparum in owl monkeys showed that all were more active than the reference compound, WR-33,063. WR-122,455, the most active derivative, and WR-171,669, ranked sixth, were selected for study in human volunteers. To assist this undertaking, appraisals of both compounds in owl monkeys infected with various strains of P. falciparum were expanded. These assessments showed: (i) that WR-122,455 was four times as active as chloroquine against infections with chloroquine-sensitive strains and that WR-171,669 equalled chloroquine in activity; (ii) that these compounds were fully active against infections with strains resistant to chloroquine, pyrimethamine, or quinine, or to all three standard drugs; (iii) that the activity of WR-122,455 was a function of total dose, single doses being as effective as the same amounts delivered in three or seven daily fractions; and (iv) that a single dose of WR-122,455 conferred extended, although only partial, protection against challenges with trophozoites. Complementary experiments in rhesus monkeys inoculated with sporozoites of P. cynomolgi showed that the activity of WR-122,455 was limited to blood schizonts and did not extend to early or late tissue schizonts. These evaluations were compatible with the results of preliminary studies of the activities of WR-122,455 and WR-171,669 in human volunteers.This publication has 31 references indexed in Scilit:
- Antimalarial Activities of Various 4-Quinolinemethanols with Special Attention to WR-142,490 (Mefloquine)Antimicrobial Agents and Chemotherapy, 1978
- Enhancement of Solubility of Drug Salts by Hydrophilic Counterions: Properties of Organic Salts of an Antimalarial DrugJournal of Pharmaceutical Sciences, 1976
- Antimalarial phenanthrene amino alcohols. 3. Halogen-containing 9-phenanthrenemethanolsJournal of Medicinal Chemistry, 1975
- Treatment of Falciparum Malaria from Vietnam with a Phenanthrene Methanol (WR 33063) and a Quinoline Methanol (WR 30090)Antimicrobial Agents and Chemotherapy, 1973
- A Phenanthrene Methanol (WR 33063) for Treatment of Acute MalariaAntimicrobial Agents and Chemotherapy, 1973
- Antimalarial phenanthrene amino alcohols. 2. Trifluoromethyl-containing 9-phenanthrenemethanolsJournal of Medicinal Chemistry, 1972
- Antimalarial activity and conformation of erythro- and threo-.alpha.-(2-piperidyl)-3,6-bis(trifluoromethyl)-9-phenanthrenemethanolJournal of Medicinal Chemistry, 1972
- Antimalarial phenathrene amino alcohols. 1. Fluorine-containing 3- and 6-substituted 9-phenanthrenemethanolsJournal of Medicinal Chemistry, 1971
- Cardiopulmonary effects of antimalarial drugs: II. PhenanthrenemethanolsToxicology and Applied Pharmacology, 1970
- THE USE OF SN-10,275 IN THE PROPHYLAXIS AND TREATMENT OF SPOROZOITE-INDUCED VIV AX MALARIA (CHESSON STRAIN) 1JCI Insight, 1948