Please use this identifier to cite or link to this item: http://repositorio.ufla.br/jspui/handle/1/35326
metadata.artigo.dc.title: Synthesis, biological evaluation and docking studies of novel bisquaternary aldoxime reactivators on acetylcholinesterase and butyrylcholinesterase inhibited by paraoxon
metadata.artigo.dc.creator: Kuca, Kamil
Jun, Daniel
Junova, Lucie
Musilek, Kamil
Hrabinova, Martina
Silva, Jorge Alberto Valle da
Ramalho, Teodorico Castro
Valko, Marian
Wu, Qinghua
Nepovimova, Eugenie
França, Tanos Celmar Costa
metadata.artigo.dc.subject: Acetylcholinesterase
Antidote
Butyrylcholinesterase
Organophosphate
Oxime
Paraoxon
metadata.artigo.dc.publisher: Molecular Diversity Preservation International (MDPI)
metadata.artigo.dc.date.issued: 7-May-2018
metadata.artigo.dc.identifier.citation: KUCA, K. et al. Synthesis, biological evaluation and docking studies of novel bisquaternary aldoxime reactivators on acetylcholinesterase and butyrylcholinesterase inhibited by paraoxon. Molecules, [S.l.], v. 23, n. 5, p. 1103-1115, 2018. DOI: 10.3390/molecules23051103.
metadata.artigo.dc.description.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.
metadata.artigo.dc.identifier.uri: http://repositorio.ufla.br/jspui/handle/1/35326
metadata.artigo.dc.language: en_US
Appears in Collections:DQI - Artigos publicados em periódicos



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