| Title : 6-Methyluracil derivatives as peripheral site ligand-hydroxamic acid conjugates: Reactivation for paraoxon-inhibited acetylcholinesterase - Semenov_2019_Eur.J.Med.Chem_185_111787 |
| Author(s) : Semenov VE , Zueva IV , Lushchekina SV , Lenina OA , Gubaidullina LM , Saifina LF , Shulaeva MM , Kayumova RM , Saifina AF , Gubaidullin AT , Kondrashova SA , Latypov SK , Masson P , Petrov KA |
| Ref : Eur Journal of Medicinal Chemistry , 185 :111787 , 2019 |
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Abstract :
New uncharged conjugates of 6-methyluracil derivatives with imidazole-2-aldoxime and 1,2,4-triazole-3-hydroxamic acid units were synthesized and studied as reactivators of organophosphate-inhibited cholinesterase. Using paraoxon (POX) as a model organophosphate, it was shown that 6-methyluracil derivatives linked with hydroxamic acid are able to reactivate POX-inhibited human acetylcholinesterase (AChE) in vitro. The reactivating efficacy of one compound (5b) is lower than that of pyridinium-2-aldoxime (2-PAM). Meanwhile, unlike 2-PAM, in vivo study showed that the lead compound 5b is able: (1) to reactivate POX-inhibited AChE in the brain; (2) to decrease death of neurons and, (3) to prevent memory impairment in rat model of POX-induced neurodegeneration. |
| PubMedSearch : Semenov_2019_Eur.J.Med.Chem_185_111787 |
| PubMedID: 31675511 |
Semenov VE, Zueva IV, Lushchekina SV, Lenina OA, Gubaidullina LM, Saifina LF, Shulaeva MM, Kayumova RM, Saifina AF, Gubaidullin AT, Kondrashova SA, Latypov SK, Masson P, Petrov KA (2019)
6-Methyluracil derivatives as peripheral site ligand-hydroxamic acid conjugates: Reactivation for paraoxon-inhibited acetylcholinesterase
Eur Journal of Medicinal Chemistry
185 :111787
Semenov VE, Zueva IV, Lushchekina SV, Lenina OA, Gubaidullina LM, Saifina LF, Shulaeva MM, Kayumova RM, Saifina AF, Gubaidullin AT, Kondrashova SA, Latypov SK, Masson P, Petrov KA (2019)
Eur Journal of Medicinal Chemistry
185 :111787