Isolation of Antiplasmodial Oxazoles and Isoflavonoids from the Roots of Oxytropis trichophysa and Total Synthesis of Oxazole-type Alkaloids.

Abstract

A chemical examination of a root extract of Oxytropis trichophysa led to the isolation and identification of 23 compounds, including oxazole-type alkaloids and isoflavonoid derivatives. Notably, three oxazole-type alkaloids (1, 2, and 3) and two isoflavonoid derivatives (7 and 10) were obtained from a natural source for the first time. In addition, O. trichophysa derived 2,5-diphenyloxazoles and their derivatives were synthesized. Despite their potential activity, the antiplasmodial activities of naturally occurring 2,5-diphenyloxazoles and certain isoflavonoids remain unexplored. Therefore, the antiplasmodial activities of both the naturally occurring and synthesized compounds were evaluated against Plasmodium falciparum strain 3D7. Among the tested compounds, three naturally occurring oxazole-type alkaloids (1, 5, and 6), one synthesized alkaloid (34), and two isoflavonoid derivatives (13 and 15) demonstrated significant inhibitory effects, with half-maximal inhibitory concentration (IC₅₀) values ranging from 3.1 to 6.2 μM and selective indices between 0.9 and 18.8. Compound 1 showed the most potent inhibitory activity, with an IC₅₀ of 3.1 μM, while its cytotoxic concentration 50% value against human foreskin fibroblasts was found to be 8.5 μM. The oxazole-type alkaloids and isoflavonoids isolated from this plant provide valuable insights into its chemical composition and may help elucidate the antiplasmodial properties of O. trichophysa.