熱帯病と公衆衛生ジャーナル

概要

Chemoprevention of Schistosomiasis: In vitro Antiparasitic Activity of Nineteen Plant-derived and Synthetic Simple Naphthoquinones and Naphthols against Schistosoma Mansoni Adult Worms

Lizandra G. Magalhães, G. Subba Rao, Ingrid A. O. Soares, Fernanda R. Badocco, Wilson R. Cunha, Vanderlei Rodrigues, and Govind J. Kapadia

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.