HPLC- based activity profiling for new antiparasitic leads: In vitro and in vivo antitrypanosomal activity of cynaropicrin

In a medium throughput screen of 880 plant and fungal extracts for antiplasmodial, antitrypanosomal and leishmanicidal activity, the dichloromethane extract of Centaurea salmantica (Asteraceae) showed strong inhibition against Trypanosoma brucei rhodesiense, the parasite causing African sleeping sickness.

HPLC-based activity profiling of this active extract [1] led to the characterisation of cynaropicrin, a guajanolide sesquiterpene lactone as the active constituent. Cynaropicrin had an IC₅₀ of 0.3µM (±0.35) against T. brucei rhodesiense in vitro. It was ten and fifteen times less active against P. falciparum (IC₅₀: 2.99±0.28) and T. cruzi (IC₅₀: 4.43±0.036). A series of similar natural and semi-synthetic guaianolides were tested similarly for preliminary structure activity studies. Mice infected with T. brucei rhodesiense were treated intraperitoneally with cynaropicrin (10mg/kg/d). After 4 days, a 98% decrease of parasitaemia was observed compared to the untreated controls. The treated test animals had 100% survival until day 14 after infection, whereas the control animals died within 12 days. Cynaropicrin is a promising new antitrypanosomal lead and the first natural sesquiterpene lactone to show activity against T.b. rhodesiense in vivo.

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References: 1. Adams, M. et al. (2009) Nat. Prod. Commun. 9: 1377–1381.