Biarylalkyl Carboxylic Acid Derivatives as Novel Antischistosomal Agents. (9th May 2016)

• Record Type: Journal Article
• Authors: Mäder, Patrick; Blohm, Ariane S.; Quack, Thomas; Lange‐Grünweller, Kerstin; Grünweller, Arnold; Hartmann, Roland K.; Grevelding, Christoph G.; Schlitzer, Martin
• Is Part Of: ChemMedChem. Volume 11:Number 13(2016)
• Page Start: 1459
• Page End: 1468
• Publication Date: 2016-05-09
• Subjects: biaryls -- carboxylic acids -- inhibitors -- parasites -- structure–activity relationships; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600127
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Parasitic platyhelminths are responsible for serious infectious diseases, such as schistosomiasis, which affect humans as well as animals across vast regions of the world. The drug arsenal available for the treatment of these diseases is limited; for example, praziquantel is the only drug currently used to treat ≥240 million people each year infected with Schistosoma spp ., and there is justified concern about the emergence of drug resistance. In this study, we screened biarylalkyl carboxylic acid derivatives for their antischistosomal activity against S. mansoni . These compounds showed significant influence on egg production, pairing stability, and vitality. Tegumental lesions or gut dilatation was also observed. Substitution of the terminal phenyl residue in the biaryl scaffold with a 3‐hydroxy moiety and derivatization of the terminal carboxylic acid scaffold with carboxamides yielded compounds that displayed significant antischistosomal activity at concentrations as low as 10 μm with satisfying cytotoxicity values. The present study provides detailed insight into the structure–activity relationships of biarylalkyl carboxylic acid derivatives and thereby paves the way for a new drug‐hit moiety for fighting schistosomiasis. Abstract : Mind your PZQs : Over 240 million people worldwide are infected by schistosomiasis. Since the 1980s, praziquantel (PZQ) has been the drug of choice for the treatment of schistosomiasis. However, long‐term use of one drug may result in drug‐resistant parasites. Therefore, we investigated the in vitro potential of biarylalkyl carboxylic acid derivatives against Schistosoma mansoni . The present study provides deep insight into structure–activity relationships.