In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models

• Published in: Drug design, development and therapy Vol. 7; no. default; pp. 1377 - 1384
• Main Authors: Schleiferböck, Sarah, Scheurer, Christian, Ihara, Masataka, Itoh, Isamu, Bathurst, Ian, Burrows, Jeremy N, Fantauzzi, Pascal, Lotharius, Julie, Charman, Susan A, Morizzi, Julia, Shackleford, David M, White, Karen L, Brun, Reto, Wittlin, Sergio
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2013; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: Animals; Antimalarial agents; antimalarial studies; Antimalarials; Antimalarials - administration & dosage; Antimalarials - pharmacokinetics; Antimalarials - pharmacology; Artemisinins - pharmacokinetics; Artemisinins - pharmacology; Artesunate; Chemical properties; cross-resistance; Dosage and administration; Dose-Response Relationship, Drug; Drug Resistance; Drug therapy; Erythrocytes; Female; Half-Life; Lead; Lead compounds; Low concentrations; Malaria; Malaria - drug therapy; Malaria - parasitology; Mice; Original Research; Oxazines - administration & dosage; Oxazines - pharmacokinetics; Oxazines - pharmacology; Plasmodium berghei; Plasmodium berghei - drug effects; Plasmodium falciparum; Plasmodium falciparum - drug effects; Pyridines - administration & dosage; Pyridines - pharmacokinetics; Pyridines - pharmacology; stage-specificity; Switzerland; Plasmodium falciparum; cross-resistance; stage-specificity; antimalarial studies
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S51298

The objective of this work was to characterize the in vitro (Plasmodium falciparum) and in vivo (Plasmodium berghei) activity profile of the recently discovered lead compound SSJ-183. The molecule showed in vitro a fast and strong inhibitory effect on growth of all P. falciparum blood stages, with a tendency to a more pronounced stage-specific action on ring forms at low concentrations. Furthermore, the compound appeared to be equally efficacious on drug-resistant and drug-sensitive parasite strains. In vivo, SSJ-183 showed a rapid onset of action, comparable to that seen for the antimalarial drug artesunate. SSJ-183 exhibited a half-life of about 10 hours and no significant differences in absorption or exposure between noninfected and infected mice. SSJ-183 appears to be a promising new lead compound with an attractive antimalarial profile.