6α-Hydroxy-α-toxicarol and (+)-tephrodin with antiplasmodial activities from Tephrosia species

Abstract

The CH2Cl2/MeOH (1:1) extract of the roots of Tephrosia villosa showed good antiplasmodial activity against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC50 values of 3.1 ± 0.4 and 1.3 ± 0.3 μg/mL, respectively. Chromatographic separation of the extract yielded a new rotenoid, 6α-hydroxy-α-toxicarol, along with five known rotenoids, (rotenone, deguelin, sumatrol, 12a-hydroxy-α-toxicarol and villosinol). Similar treatment of the extract of the stem of Tephrosia purpurea (IC50 = 4.1 ± 0.4 and 1.9 ± 0.2 μg/mL against D6 and W2 strains of P. falciparum, respectively) yielded a new flavone having a unique substituent at C-7/C-8 [trivial name (+)-tephrodin], along with the known flavonoids tachrosin, obovatin methyl ether and derrone. The relative configuration and the most stable conformation in (+)-tephrodin was determined by NMR and theoretical energy calculations. The rotenoids and flavones tested showed good to moderate antiplasmodial activities (IC50 = 9 − 23 μМ). Whereas the cytotoxicity of rotenoids is known, the flavones (+)-tephrodin and tachrosin did not show significant cytotoxicity (IC50 > 100 μМ) against mammalian African monkey kidney (vero) and human larynx carcinoma (HEp2) cell lines.