Anti-protozoal and structure-activity relationships of chemical constituents of Acridocarpus chloropterus Oliver (Malpighiaceae) from Tanzania

Abstract

Chromatographic separation of Acridocarpus chloropterus extract led to the isolation and identification of five triterpenes: β-sitosterol (1), stigmasterol (2), friedelin (3), oleanolic acid (4), ursolic acid (5); and five flavonoids: apigenin (6), luteolin (7), vitexin (8), kaempferol (9) and quercetin (10). Quercetin (10) exhibited moderate in vitro anti-plasmodial activity (IC50 2.6+0.05 μg/ml) while the rest of compounds were inactive. Mild to weak in vitro anti-trypanosomal activity was observed in quercetin (10) (IC50 3.60+0.1 μg/ml), ursolic acid (5) (IC50 7.80+0.1 μg/ml) and apigenin (6) (IC50 9.0+0.1 μg/ml). Ursolic acid (5) exhibited strong in vitro anti-leishmanial activity (IC50 0.80+0.001 μg/ml) while oleanolic acid (4), apigenin (6), kaempferol (9) and quercetin (10) showed moderate to mild activity (2.10+0.1, 2.20+0.1, 5.90+ 0.1 and 3.5+0.2 μg/ml, respectively) whereas favorable selectivity was observed with all flavonoids. Structure-activity-relationship (SAR) comparison of the isolated triterpenoids confirmed that the hydroxyl group at C-3 together with C-23, C-25, C-26 and C-30 methyl groups, C-12/C-13 double bond, the C-28 carboxylic acid group, and H-20 in ursolic acid (5) and related compounds are all responsible for the strong anti-leishmanial activity. The 3-OH and 3′-OH in the apigenin (6) and related compounds are responsible for the strong anti-protozoal activity observed in the isolated flavonoids. The strong to moderate anti-leishmanial activity of the isolated triterpenes and flavonoids make them good candidates or templates for new anti-protozoal drug devel