Abstract
Schistosomiasis, a debilitating disease dating back to ancient times, is currently endemic in 78 tropical and subtropical countries with 243 million people requiring treatment. Current treatment of schistosomiasis depends primarily on a single drug, praziquantel which is less effective against larval stage of the parasite and has potential for development of resistance. Thus, there is urgent need for development of new, effective and inexpensive antischistosomal drugs. Simple naphthoquinone (NAPQ) secondary metabolites in plants are known to act as phytotoxins in preventing bacterial, fungal and parasitic attacks. The present study reports antischistosomal activity of nineteen plant-derived and synthetic simple NAPQs and naphthols against Schistosoma mansoni adult worms under in vitro conditions. Four of the tested compounds met the WHO’s Special Program for Research and Training in Tropical Diseases (TDR) in vitro criterion for “hit” and lead compound (100% mortality of adult worms at a concentration of ≤ 5 µg/ml when incubated for 48 h): plant-derived naphthazarin, two synthetic NAPQs, 1, 4-NAPQ and 2-methy-1, 4-NAPQ (menadione) and synthetic 1-amino-2-naphthol hydrochloride. Structure-antischistosomal activity studies with 1, 4-NAPQs indicated the importance of the number and position of hydroxyl and methyl groups, particularly at C-2, C-5 and C-8 positions of the parent NAPQ molecule, which play important role in stabilizing quinone moiety and formation of reactive oxygen species essential for antiparasitic effect. The results call for further in vivo studies on the chemopreventive potential of plant-derived naphthazarin and synthetic 1,4-NAPQ, menadione and 1-amino-2-naphthol, all of which have met the WHO/TDR in vitro criterion for their consideration as lead schistosomicidal candidates.
Highlights
Schistosomiasis is a tropical disease caused by trematodes of the genus Schistosoma [1] and World Health Organization (WHO) considers this water-borne, communicable disease a major public health problem of the 21st century [2]
The nineteen plant-derived and synthetic NAPQ and naphthol compounds (Figure 1) were tested at 100 μM concentration and the following ten compounds (52.6% of compounds tested) were found to cause death of 100% of adult S. mansoni worms when incubated for 24 h (Table 1): two plant-derived 1,4-NAPQs, naphthazarin (NAP-2) and juglone (NAP-3); synthetic analogs, five 1,4-NAPQs (NAP-5, NAP-6, NAP-8, NAP-9 and NAP10); 1,2-NAPQ–4-sulfonic acid (NAP-15) and two 1-amino-naphthols (NAP-16 and NAP-17)
The present investigation is a continuation of our research on antiparasitic activity of NAPQs which compares antischistosomal activity of nineteen plant-derived and synthetic simple NAPQs and naphthols (Figure 1) against S. mansoni adult worms under in vitro experimental conditions
Summary
Schistosomiasis is a tropical disease caused by trematodes of the genus Schistosoma [1] and World Health Organization (WHO) considers this water-borne, communicable disease a major public health problem of the 21st century [2]. There is evidence that it was prevalent in ancient Egypt as early as 1250-1000 BC by the discovery of calcified schistosomes eggs in the kidneys of mummies [4]. Similar discoveries have been made with Chinese mummies dating back to 400 BC [5]. It was first described as a tropical parasitic disease by the German physician Theodore Maximillian Bilharz in 1851 while working in a Cairo hospital [6]. The larvae develop into adult schistosomes and the females release eggs in the blood vessels. Adult S. mansoni parasites can survive in the mesenteric veins and enter the hepatic portal circulation system for up to 30 years without being eliminated by the immune attack in their human host [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
