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oai:figshare.com:article/34024080 2026-09-29T13:41:50Z category_4 category_7 category_8 category_12 category_13 category_19 category_272 category_106 category_734 category_135 portal_63 item_type_6 month_year_09_2026

Synthesis and Antischistosomal Activity Profile of Several Sub-Series of Redox-Active Lead 3‑BenzylmenadionesInvestigations of the Modes of Action in Yeast Jeremy Pecourneau (25137288) Jimmy Richard (6068525) Brigitte Meunier (19685) Maude Dagenais (25137291) Cécile Häberli (6184631) David L. Williams (85105) Jennifer Keiser (39606) Elisabeth Davioud-Charvet (31519) Biochemistry Medicine Microbiology Cell Biology Genetics Pharmacology Environmental Sciences not elsewhere classified Science Policy Biological Sciences not elsewhere classified Computational Biology two drug targets respiratory growth defect recombinant drug target new antischistosomal agents antischistosomal activity profile per os </ yeast nadh dehydrogenase ex vivo </ 50 </ sub yeast three sub vivo </ moderate activity several sub mansoni </ yeast model synthase inhibition potential source potent representatives possible mode oxidative stress glutathione reductase exhibited ic events responsible called schistodiones benzoylmenadione metabolites active compounds 5 μm Three sub-series of 3-benzylmenadiones were discovered as new antischistosomal agents. The most potent representatives, called schistodiones, exhibited IC50 values <5 μM against larvae and ex vivo Schistosoma mansoni adult worms and moderate activity per os in the S. mansoni-infected mouse model in vivo. We synthesized the putative 3-benzoylmenadione metabolites of the most active compounds and explored the possible mode(s) of action using the yeast model and the recombinant drug target S. mansoni thioredoxin-glutathione reductase. Two drug targets were identified in yeast: the yeast NADH dehydrogenase and Cox15, involved in events responsible for respiratory growth defect in yeast, respectively: (i) the bioreductive activation step producing reactive oxygen species and (ii) the heme a synthase inhibition. These two drug targets are discussed in the context of S.mansoni biology, with S. mansoni thioredoxin–glutathione reductase redox-cycling and a potential source of oxidative stress in the parasite. 2026-09-29T00:00:00Z Text Journal contribution 10.1021/acsomega.6c06911.s001 https://figshare.com/articles/journal_contribution/Synthesis_and_Antischistosomal_Activity_Profile_of_Several_Sub-Series_of_Redox-Active_Lead_3_Benzylmenadiones_Investigations_of_the_Modes_of_Action_in_Yeast/34024080 CC BY-NC 4.0