Summary /

Compounds were dissolved in dimethylsulfoxide (DMSO) and added at concentrations indicated to freshly perfused worms in RPMI 1640 containing 25 mM HEPES, pH 7, 150 units/ml penicillin, 125 mg/ml streptomycin and 10% FCS (Cell Grow, Fisher). Media were replaced every 2 d with fresh media with the compounds added at the designated concentrations. Control worms were treated with equal amounts of DMSO alone. Worms were subsequently observed for motility and mortality and collected at the indicated times for analysis. Worms were homogenized by sonication in PBS, and homogenates were assayed for enzyme activities as described. To assess the importance of NO production, the potassium salt of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO, Invitrogen), a NO scavenger, was dissolved in water and incubated with freshly perfused S. mansoni worms at 100 mM in the presence or absence of 10 mM SID 11111612.

Results showed 100% inhibition of parasitic survival after 24 hours. The anti-schistosomal activity of ML002 is concomitant with NO production; however, other unrelated NO donors did not have an effect against Schisto worms.

Summary /

ML002 was dissolved in DMSO and administrated by intraperitoneal injection at 10 mg/kg (mpk) daily for five consecutive days during the development of S.mansoni in the mouse. Large and highly significant reductions in worm burdens were observed from 3 experimental treatments: (1) skin/lung stage larvae; (2) juvenile liver-stage worm; (3) adult egg-laying parasite. A DMSO treated infected mice was used as a control.

Results showed that worms recovered from treatment 2 are small and stunted (specially males) relative to the worms recovered from untreated mice. Gross anatomy of the liver from the ML002 treated mice showed decrease liver granuloma resulting from host immunological reaction against trapped parasite eggs.