Phytochemical Investigation Of Tephrosia Rhodesica And Tephrosia Polyphylla For Antiplasmodial Principles.

Abstract

The increasing problem of drug resistance of malaria parasites, adverse side effects and the question of affordability to the inhabitants of developing countries, call for different interventions including search for new antiplasmodial lead compounds. In this regard, higher plants remain a reservoir of secondary metabolites with antiplasmodial properties. It is in this context that the present research was set up to investigate Tephrosia rhodesica Baker and Tephrosia polyphylla (Chiov.) Gillet for antiplasmodial agents against Plasmodium falciparum which is the major cause of malaria in humans. The roots and seed pods of Tephrosia rhodesica and stems of Tephrosia polyphylla were dried, ground and then extraction was done using dichloromethane to methanol in the ratio of 1:1 at 24 oC. The crude extracts were loaded to column and various methods of purification applied like preparative TLC, crystallization, HPLC and circular chromatography. From these two Tephrosia species ten compounds, including two new compounds were isolated. Six compounds from roots of T. rhodesica including one new compound, named rhodbenzofuran (86) were obtained. From the seedpods of T. rhodesica, a new compound, named rhodflavononol (87) was isolated together with a known compound and two known compounds were isolated from stems of T. polyphylla. A synthetic oxime, named candidone-oxime (94), was also prepared from candidone (91). Isolated compounds were characterized using various methods such as 1D-NMR (1H-NMR and 13C-NMR), 2D-NMR (HH COSY, NOESY,TOCSY, HMBC and HSQC), X-ray Crystallography, UV, CD and mass spectrometry. The crude extracts and compounds isolated from them were tested for antiplasmodial activities against different strains of P. falciparum, namely chloroquine resistant clone (W2) and chloroquine sensitive clones (3D7 and D6). The tests showed that candidone (91) was the most active compound against chloroquine resistance clone W2 (IC50 = 1.2±0.1μM) and chloroquine sensitive clone 3D7 (IC50 = 3.5μM). Over all, the study has showed that the two Tephrosia species elaborate flavonoid derivatives, some of which showing good antiplasmodial activities.