Effects of monepantel, albendazole, levamisole, and pyrantel pamoate on <i>T. muris in vivo</i>.

<p>SD = standard deviation.</p>§<p>Mann-Whitney U test comparing the median of the worm burdens of control and treated mice.</p

Dose response relationships of monepantel, albendazole, levamisole, and pyrantel pamoate on <i>A. ceylanicum in vivo</i>.

<p>SD = standard deviation. The numbers in superscript refer to the corresponding control group.</p><p>*Kruskal Wallis test comparing the median of the worm burdens of control and treated hamsters (all doses versus control),</p>§<p>Mann-Whitney U-test comparing the median of the worm burdens of control and treated hamsters (one dose versus control).</p

Additional file 1: of Controlling schistosomiasis with praziquantel: How much longer without a viable alternative?

Multilingual abstracts in the five official working languages of the United Nations. (PDF 466 kb

Effects of monepantel and albendazole on <i>A. suum in vivo</i>.

<p>SD = standard deviation.</p>§<p>Mann-Whitney U test comparing the median of the worm burdens of control and treated mice.</p

Effects of monepantel and albendazole on <i>N. americanus in vivo</i>.

<p>SD = standard deviation.</p><p>*Kruskal Wallis test comparing the median of the worm burdens of control and treated hamsters (all doses versus control).</p

50% inhibitory concentrations of monepantel, albendazole, levamisole, and pyrantel pamoate on <i>A. ceylanicum</i>, <i>N. americanus</i>, and <i>T. muris</i>.

<p>IC₅₀s (µg/ml) were calculated for monepantel, albendazole, levamisole, and pyrantel pamoate after 72 h on L3 and adult stages of <i>A. ceylanicum</i>, <i>N. americanus</i>, and <i>T. muris</i>. r = linear correlation coefficient of the median-effect plot, indicating the goodness of fit. r≥0.85 indicates a satisfactory fit. n.d.: not determined, fitting not possible.</p

Ovicidal activity of monepantel, albendazole, levamisole, and pyrantel pamoate on <i>A. ceylanicum</i> eggs.

<p>SD = standard deviation.</p><p>*P-value <0.001 (Fisher's exact test).</p

Analysis of the Physicochemical Properties of Anti-Schistosomal Compounds to Identify Next-Generation Leads

To investigate the physicochemical properties of anti-schisto­somal compounds reported between 2008 and 2023, a simple but extensive literature scrutiny was conducted. Keywords were searched in Chemical Abstracts Service (CAS) SciFinder and primary medicinal chemistry and pharmacology literature to locate publications with compounds displaying ex vivo and/or in vivo anti-schisto­somal activity. A total of 57 repurposed U.S. Food and Drug Administration (FDA)-approved drugs, hits and their derivatives were manually extracted, curated and compared to known anti-schisto­somal oral drugs in view of establishing trends of calculated critical molecular properties. From this analysis, it was determined that more than 65% of the compounds display cLogD7.4 > 3 values, whereas oxamniquine, metrifonate and praziquantel (PZQ), previous and currently used oral anti-schisto­somal drugs, possess lower cLogD7.4 values (≤2.5). Furthermore, the lipophilicity associated with PZQ corresponds to a highly permeable and sparingly soluble compound, characteristics that favor drug absorption and compound penetration in the parasite. These physicochemical properties together with PZQ’s anti-schisto­somal activity make PZQ an essential medicine for the treatment of schisto­somiasis and demonstrate the importance of finding the right balance among potency (e.g., EC50 < 5 and 0.5 μM), cell permeability (e.g., Papp > 2 × 106 cm/s) and kinetic aqueous solubility (e.g., >10 μM) to provide high-quality hits and/or leads for the discovery of new oral anti-schisto­somal therapeutics

Analysis of the Physicochemical Properties of Anti-Schistosomal Compounds to Identify Next-Generation Leads

To investigate the physicochemical properties of anti-schisto­somal compounds reported between 2008 and 2023, a simple but extensive literature scrutiny was conducted. Keywords were searched in Chemical Abstracts Service (CAS) SciFinder and primary medicinal chemistry and pharmacology literature to locate publications with compounds displaying ex vivo and/or in vivo anti-schisto­somal activity. A total of 57 repurposed U.S. Food and Drug Administration (FDA)-approved drugs, hits and their derivatives were manually extracted, curated and compared to known anti-schisto­somal oral drugs in view of establishing trends of calculated critical molecular properties. From this analysis, it was determined that more than 65% of the compounds display cLogD7.4 > 3 values, whereas oxamniquine, metrifonate and praziquantel (PZQ), previous and currently used oral anti-schisto­somal drugs, possess lower cLogD7.4 values (≤2.5). Furthermore, the lipophilicity associated with PZQ corresponds to a highly permeable and sparingly soluble compound, characteristics that favor drug absorption and compound penetration in the parasite. These physicochemical properties together with PZQ’s anti-schisto­somal activity make PZQ an essential medicine for the treatment of schisto­somiasis and demonstrate the importance of finding the right balance among potency (e.g., EC50 < 5 and 0.5 μM), cell permeability (e.g., Papp > 2 × 106 cm/s) and kinetic aqueous solubility (e.g., >10 μM) to provide high-quality hits and/or leads for the discovery of new oral anti-schisto­somal therapeutics

Mean (SE) fecal larvae output of 4 <i>S. ratti</i>-infected rats that remained untreated and 4 <i>S. ratti</i>-infected rats that were treated on day 5 post-exposure with either 0.5 mg/kg ivermectin, or either 50, 100 or 200 mg/kg tribendimidine.

<p>Mean (SE) fecal larvae output of 4 <i>S. ratti</i>-infected rats that remained untreated and 4 <i>S. ratti</i>-infected rats that were treated on day 5 post-exposure with either 0.5 mg/kg ivermectin, or either 50, 100 or 200 mg/kg tribendimidine.</p