Lignans, Amides, and Saponins fromHaplophyllum tuberculatumand Their Antiprotozoal Activity

Abstract

A screening of Sudanese medicinal plants for antiprotozoal activities revealed that the chloroform and water fractions of the ethanolic root extract ofHaplophyllum tuberculatumexhibited appreciable bioactivity againstLeishmania 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 saponins11-13. Compounds1,2, and5-13are reported for the first time fromHaplophyllumspecies 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 againstLeishmania donovaniamastigotes,Plasmodium falciparum,andTrypanosoma brucei rhodesiensebloodstream forms, along with their cytotoxicity to rat myoblast L6 cells. Nectandrin B (2) exhibited the highest activity againstL. donovani(IC(50)4.5 mu M) and the highest selectivity index (25.5).