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.
- MeSH
- acetylcholinesterasa chemie MeSH
- antidota chemická syntéza farmakologie MeSH
- butyrylcholinesterasa chemie MeSH
- cholinesterasové inhibitory chemie MeSH
- enzymatické testy MeSH
- erytrocyty účinky léků enzymologie MeSH
- insekticidy antagonisté a inhibitory chemie toxicita MeSH
- interakční proteinové domény a motivy MeSH
- lidé MeSH
- obidoxim chlorid chemie farmakologie MeSH
- oximy chemická syntéza farmakologie MeSH
- paraoxon antagonisté a inhibitory chemie toxicita MeSH
- reaktivátory cholinesterázy chemická syntéza farmakologie MeSH
- sekundární struktura proteinů MeSH
- simulace molekulového dockingu MeSH
- termodynamika MeSH
- vazba proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
