Fig 1.
Chemical structure of EPIIS alkaloid with its heteroatoms and stereoisomer annotated.
EPIIS possesses 39 atoms (C16H18O3N2).
Fig 2.
(A) pseudomolecular ion with m/z 286.9 Da [M + H]+. (B) MS2 fragments with m/z 268.8 Da [M—H2O + H]+ e 180,7 Da.
Fig 3.
Effect on worm burden of a single oral dose of EPIIS administered to mice harboring a 60-day-old adult S. mansoni infection, stratified by sex.
Points represent data from individual mice that were infected and treated with EPIIS, or infected and untreated (control). Each treated group was compared to its corresponding untreated group. The horizontal bars represent median values. *P < 0.05, **P < 0.01, ***P < 0.001 compared with untreated groups.
Fig 4.
Effect on egg development and on Stoll egg count of a single dose 100 mg/kg of EPIIS administered to mice harboring a 60-day-old adult S. mansoni infection.
(A) EPIIS effect on egg development stages (oogram) (B) Effect on Stoll egg count. Points represent data from individual mice that were infected and treated with EPIIS, or infected and untreated (control). The horizontal bars represent median values. **P < 0.01 and ***P < 0.001 compared with untreated groups.
Fig 5.
Effect of EPIIS on relative liver and spleen weights.
Points represent data from individual mice that were infected and treated with EPIIS or were infected and untreated (control). The horizontal bars represent median values. *P < 0.05 and **P < 0.01 compared with untreated groups.
Fig 6.
Scanning electron microscopy of S. mansoni adults retrieved 48 h after treatment with EPIIS (100 mg/kg).
A-D: Control group—untreated; E–L: Male and female worms. The arrows show damage to tegument with reduction in the size of the spines, and damage to the oral and ventral suckers in male worms, followed by body corrugation in female worms. Image bar scale: (A) 100X___10 kv; (B) 120X ___10 kv; (C-D) 180X ___10 kv; (E-F) 127X ___10 kv; (G-H) 250X___10 kv; (I- L) 350X___10 kv.
Fig 7.
Antischistosomal effect of a single 100 mg/kg oral dose of EPIIS administered to mice harboring juvenile S. mansoni infection.
(A) EPIIS effect on worm burden. (B) EPIIS effect on egg development stages (oogram) (C) Effect on Stoll egg count. Points represent data from individual mice that were infected and treated with EPIIS, or infected and untreated (control). The horizontal bars represent median values. **P < 0.01 and ***P < 0.001 compared with untreated groups.
Table 1.
Physicochemical parameters through in silico analysis of EPIIS using pkCSM methodology.
Table 2.
In silico analysis of toxicological properties of EPIIS predicted using the pkCSM methodology.
Fig 8.
In vitro cytotoxicity assay with EPIIS.
Adhesion indices of NIH-3T3 and HaCaT cells treated with EPIIS. The concentrations of EPIIS were 32 or 512 μg/mL and the adhered cell rates were measured every 30 min for 137 h.
Table 3.
Hematological parameters of Swiss mice treated with EPIIS by oral route.
Table 4.
Biochemical parameters in sera obtained from Swiss mice treated with EPIIS by oral route.
Fig 9.
Photomicrographs of histological sections of liver (A1, A2), spleen (B1, B2), kidney (C1, C2), lung (D1, D2) and brain (E1, E2) obtained from Swiss mice of control group (first column) and group treated with 2000 mg/kg EPIIS (second column). Hematoxylin & eosin, 400 X magnification, bars = 50 μm.