Lignans, Amides, and Saponins from Haplophyllum tuberculatum and Their Antiprotozoal Activity.

Abdelhalim Babiker Mahmoud,Marcel Kaiser,Matthias Hamburger,Pascal Mäser,Sami Khalid,Sohee Han,Won Keun Oh,Ombeline Danton,Shereen Abd Algaffar,Aitor Moreno

doi:10.3390/molecules25122825

Abstract

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 B2 (3) and fragransin B1 (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 (IC50 4.5 µM) and the highest selectivity index (25.5).

Highlights

Neglected tropical diseases (NTDs) are a group of infectious diseases that are prevalent in tropical and sub-tropical developing countries
NTDs are strongly associated with poverty, and of high socio-economic impact
NTDs account for 48 million disability-adjusted life years (DALYs) and

Summary

Introduction

Neglected tropical diseases (NTDs) are a group of infectious diseases that are prevalent in tropical and sub-tropical developing countries. NTDs are strongly associated with poverty, and of high socio-economic impact. NTDs account for 48 million disability-adjusted life years (DALYs) and. 152,000 deaths per year [1,2]. The NTD leishmaniasis, caused by Leishmania spp., imposes a global burden of 3.3 million DALYS and 51,600 annual deaths [1,2]. There is no vaccine, and current drugs are problematic given their serious adverse effects and the emergence of drug-resistant parasites [3]. There is one efficient and safe drug, AmBisome, a liposomal formulation of amphotericin B [4].

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