Premium
Biarylalkyl Carboxylic Acid Derivatives as Novel Antischistosomal Agents
Author(s) -
Mäder Patrick,
Blohm Ariane S.,
Quack Thomas,
LangeGrünweller Kerstin,
Grünweller Arnold,
Hartmann Roland K.,
Grevelding Christoph G.,
Schlitzer Martin
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600127
Subject(s) - moiety , carboxylic acid , schistosomiasis , schistosoma mansoni , praziquantel , schistosoma , drug , combinatorial chemistry , chemistry , drug discovery , pharmacology , biology , stereochemistry , biochemistry , helminths , immunology
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 μ m 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.