Kuca_2018_Molecules_23_

Reference

Title : Synthesis, Biological Evaluation, and Docking Studies of Novel Bisquaternary Aldoxime Reactivators on Acetylcholinesterase and Butyrylcholinesterase Inhibited by Paraoxon - Kuca_2018_Molecules_23_
Author(s) : Kuca K , Jun D , Junova L , Musilek K , Hrabinova M , da Silva JAV , Ramalho TC , Valko M , Wu Q , Nepovimova E , Franca TCC
Ref : Molecules , 23 : , 2018
Abstract :

Nerve agents and oxon forms of organophosphorus pesticides act as strong irreversible inhibitors of two cholinesterases in the human body: acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8), and are therefore highly toxic compounds. For the recovery of inhibited AChE, antidotes from the group of pyridinium or bispyridinium aldoxime reactivators (pralidoxime, obidoxime, HI-6) are used in combination with anticholinergics and anticonvulsives. Therapeutic efficacy of reactivators (called “oximes”) depends on their chemical structure and also the type of organophosphorus inhibitor. Three novel oximes (K131, K142, K153) with an oxime group in position four of the pyridinium ring were designed and then tested for their potency to reactivate human (Homo sapiens sapiens) AChE (HssACHE) and BChE (HssBChE) inhibited by the pesticide paraoxon (diethyl 4-nitrophenyl phosphate). According to the obtained results, none of the prepared oximes were able to satisfactorily reactivate paraoxon-inhibited cholinesterases. On the contrary, extraordinary activity of obidoxime in the case of paraoxon-inhibited HssAChE reactivation was confirmed. Additional docking studies pointed to possible explanations for these results.

PubMedSearch : Kuca_2018_Molecules_23_
PubMedID: 29735900

Related information

Reactivator K131    K142    K153    K117

Citations formats

Kuca K, Jun D, Junova L, Musilek K, Hrabinova M, da Silva JAV, Ramalho TC, Valko M, Wu Q, Nepovimova E, Franca TCC (2018)
Synthesis, Biological Evaluation, and Docking Studies of Novel Bisquaternary Aldoxime Reactivators on Acetylcholinesterase and Butyrylcholinesterase Inhibited by Paraoxon
Molecules 23 :

Kuca K, Jun D, Junova L, Musilek K, Hrabinova M, da Silva JAV, Ramalho TC, Valko M, Wu Q, Nepovimova E, Franca TCC (2018)
Molecules 23 :