Lignans, amides, and saponins from Haplophyllum tuberculatum and their antiprotozoal activity

A screening of Sudanese medicinal plants for antiprotozoal activities revealed that the chloroform and water fractions of the ethanolic root extract of; Haplophyllum tuberculatum; exhibited appreciable bioactivity against; Leishmania donovani; . The antileishmanial activity was tracked by HPLC-based activity profiling, and eight compounds were isolated from the chloroform fraction. These included lignans tetrahydrofuroguaiacin B (; 1; ), nectandrin B (; 2; ), furoguaiaoxidin (; 7; ), and 3,3'-dimethoxy-4,4'-dihydroxylignan-9-ol (; 10; ), and four cinnamoylphenethyl amides, namely dihydro-feruloyltyramine (; 5; ), (; E; )-; N; -feruloyltyramine (; 6; ),; N; ,; N; '-diferuloylputrescine (; 8; ), and 7'-ethoxy-feruloyltyramine (; 9; ). The water fraction yielded steroid saponins; 11; -; 13; . Compounds; 1; ,; 2; , and; 5; -; 13; are reported for the first time from; Haplophyllum; species and the family Rutaceae. The antiprotozoal activity of the compounds plus two stereoisomeric tetrahydrofuran lignans-fragransin B; 2; (; 3; ) and fragransin B; 1; (; 4; )-was determined against; Leishmania donovani; amastigotes,; Plasmodium falciparum,; and; Trypanosoma brucei rhodesiense; bloodstream forms, along with their cytotoxicity to rat myoblast L6 cells. Nectandrin B (; 2; ) exhibited the highest activity against; L. donovani; (IC; 50; 4.5 µM) and the highest selectivity index (25.5).