engleski

Characterisation of uncharged oximes as antidotes in organophosphorus compounds poisoning

Defining an efficient therapy for highly toxic organophosphorus (OP) compounds poisoning is an ongoing challenge. Our recent investigations, ranging from in silico and in vitro to in vivo experiments, set guidelines for the synthesis of new compounds to act as more efficient antidotes in OP compound poisoning. A part of our research indicated that the potential benefits could be observed by introducing uncharged compounds with especially designed structures to comply with the specificities of the cholinesterase active site. Here, we present data obtained in in vitro studies on one set of newly-synthesized uncharged oximes. To assess the strengths and weaknesses of their antidotal potencies, we defined their physiological and chemical properties and linked them to their interactions with the human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Furthermore, we performed detailed kinetics studies on the reactivation of different OP-inhibited AChE and BChE by these oximes to see whether any of them could be pointed out as a promising candidate for in vivo studies. Acknowledgment: This work was supported by the Croatian Science Foundation (Grant No. 4307) and two COGITO Croatian-French bilateral grants (2013-2014 PIs: M. Katalinić and F. Nachon ; 2014-2015 PIs: Z. Kovarik and L. Jean).

acetylcholinesterase ; butyrylcholinesterase ; oximes ; kinetic ; OP

nije evidentirano