Antiplasmodial evaluation and pharmacomodulation of lanaroflavone, a biflavonoid isolated from Campnosperma panamense Standl. (Anacardiaceae)

Activity-guided fractionation of the leaves from Campnosperma panamense Standl. (Anacardiaceae) was undertaken as a part of a screening program to search new antiprotozoal drugs¹. The biflavonoid lanaroflavone was isolated and showed high in vitro antiplasmodial activity against Plasmodium falciparum erythrocytic stages and mild activity against Leishmania donovani amastigotes, but was inactive against Chaga's disease vector, Trypanosoma cruzi ^2,3. A possible machanism underlying antiplasmodial activity implicating inhibition of beta-hematin formation by this compound was supported by in vitro tests. The screening of eight natural biflavonoids structurally related to lanaroflavone allowed us to identify the nature and the length of the interflavonoid linkage as of high relevance regarding antiplasmodial activity. Thus, a serie of new flavone derivatives was synthetized and tested against P. falciparum resistant strains (K1, 7G8). They were also tested on their cytotoxicity effects upon mouse hepatocyte and L6 cells. One new aminated flavone derivative showed significant activity in the nanomolar range and very satisfying selectivity indexes (IC₅₀=80nM, SI>100), as well as absence of hemolytic effect indicating selective antiplasmodial activity. The importance of the hydrophylic framework attached at the C8 of the flavone is presently explored. The most promising derivatives will be evaluated in vivo in P. berghei infected mice.

References: 1. Weniger et al. 2001J. Ethnopharmacol. 78:193–200.

2. Weniger et al 2004 Fitoterapia 75:764–7.

3. Weniger et al 2006 Phytomedicine 13:176–180.