Silver(<scp>i</scp>) complexes with different pyridine-4,5-dicarboxylate ligands as efficient agents for the control of cow mastitis associated pathogens
Tina P. Andrejević, Dušan Milivojević, Biljana Đ. Glišić, Jakob Kljun, Nevena Lj. Stevanović, Sandra Vojnović, Strahinja Medić, Jasmina Nikodinović‐Runić, Iztok Turel, Miloš I. Djuran
Abstract
(5), py-2py is dimethyl 2,2'-bipyridine-4,5-dicarboxylate, py-2metz is dimethyl 2-(4-methylthiazol-2-yl)pyridine-4,5-dicarboxylate and py-2tz is dimethyl 2-(thiazol-2-yl)pyridine-4,5-dicarboxylate, were synthesized, structurally characterized and assessed for in vitro antimicrobial activity using both standard bioassay and clinical isolates from a contaminated milk sample obtained from a cow with mastitis. These complexes showed remarkable activity against the standard panel of microorganisms and a selection of clinical isolates from the milk of the cow diagnosed with mastitis. With the aim of determining the therapeutic potential of silver(i) complexes, their toxicity in vivo against the model organism, Caenorhabditis elegans (C. elegans), was investigated. The complexes that had the best therapeutic profile, 2 and 5, induced bacterial membrane depolarization and the production of reactive oxygen species (ROS) in Candida albicans cells and inhibited the hyphae as well as the biofilm formation. Taken together, the presented data suggest that the silver(i) complexes with pyridine ligands could be considered for the treatment of microbial pathogens, which are causative agents of cow mastitis.