In vivo Antimalarial and Antitrypanosomal Activity of Strychnogucine B, a Bisindole Alkaloid from Strychnos icaja

Abstract

Strychnogucine B is a bisindole alkaloid previously isolated from <i>Strychnos icaja</i> that possesses promising <i>in vitro</i> antiplasmodial properties. This compound was synthesized in four steps from (-)-strychnine. As no acute toxicity was observed at the highest tested cumulative dose of 60 mg/kg, its <i>in vivo</i> antimalarial activity was determined intraperitoneally at 30 mg/kg/d in a <i>Plasmodium berghei</i> murine model. In the Peters's 4-d suppressive test, this alkaloid suppressed the parasitaemia by almost 36% on day 5 and 60% on day 7 compared to vehicle-treated mice. In addition to this interesting antimalarial activity, it showed moderate <i>in vitro</i> antitrypanosomal activity but no <i>in vivo</i> activity in an acute <i>Trypanosoma brucei</i> model. It was also inactive <i>in vitro</i> on <i>Leishmania mexicana</i> promastigotes. This highlights its selective antimalarial efficacy and leads to further investigation to assess its potential as new antimalarial lead compound.