Anti-schistosomal Biarylalkyl Carboxylic Acids Amides: Development and Target-Identification
Final Report Abstract
Schistosomiasis is still one of the most important parasitic infections worldwide with an alarmingly limited therapeutic arsenal. Therefore, drug development against schistosomiasis is mandatory. Previous work of our groups identified biarylalkyl carboxylic amides with antischistosomal effects against cultured worm pairs at 10 µM. In this now finalized project, extensive variations of the basic structure have been synthesized and yielded much more additional information according to structure-activity relationships. However, none of these compounds significantly enhanced anti-schistosomal acitivity. Based on docking studies, aldose reductase (SmAR) of Schistosoma mansoni was ruled out as target structure of this class of compounds. Furthermore, a ligand-based approach delivered a number of inhibitors against SmAR, which showed different affinities in an enzyme assay established in this project. However, the inhibitors failed to cause significant anti-schistosomal activity against worm pairs in vitro. Therefore, SmAR appears to be no valid target for further drug development. In summary, this approach can be considered as finished.
Publications
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Synthese und in vitro-Testung von Biarylalkylcarbonsäure- und Ebselen-Derivaten gegen Schistosoma mansoni, Dissertation, Marburg, 2020.
A. M. Peter Ventura
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Synthesis and antischistosomal activity of linker‐ and thiophene‐modified biaryl alkyl carboxylic acid derivatives. Archiv der Pharmazie, 354(12).
Peter Ventura, Alejandra M.; Haeberlein, Simone; Konopka, Leonie; Obermann, Wiebke; Grünweller, Arnold; Grevelding, Christoph G. & Schlitzer, Martin
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Entwicklung von Biarylalkylcarbonsäure- und Indol-Derivaten als potenzielle anthelminthische Wirkstoffe gegen Schistosoma mansoni, Dissertation, Marburg.
S. Reul
