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Glycosylated-imidazole aldoximes as reactivators of pesticides inhibited AChE: Synthesis and in-vitro reactivation study

R. Sharma, K. Upadhyaya, B. Gupta, KK. Ghosh, RP. Tripathi, K. Musilek, K. Kuca

. 2020 ; 80 (-) : 103454. [pub] 20200706

Language English Country Netherlands

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc21011923

The present armamentarium of commercially available antidotes provides limited protection against the neurological effects of organophosphate exposure. Hence, there is an urgent need to design and develop molecules that can protect and reactivate inhibited-AChE in the central nervous system. Some natural compounds like glucose and certain amino acids (glutamate, the anion of glutamic acid) can easily cross the blood brain barrier although they are highly polar. Glucose is mainly transported by systems like glucose transporter protein type 1 (GLUT1). For this reason, a series of non-quaternary and quaternary glycosylated imidazolium oximes with different alkane linkers have been designed and synthesized. These compounds were evaluated for their in-vitro reactivation ability against pesticide (paraoxon-ethyl and paraoxon-methyl) inhibited-AChE and compared with standards antidote AChE reactivators pralidoxime and obidoxime. Several physicochemical properties including acid dissociation constant (pKa), logP, logD, HBD and HBA, have also been assessed for reported compounds. Out of the synthesized compounds, three have exhibited comparable potency with a standard antidote (pralidoxime).

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$a Upadhyaya, Kapil $u Department of Pharmaceutical and Biomedical Sciences, University of Georgia, 250 West Green Street, Athens, GA 30602, USA
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$a Gupta, Bhanushree $u Centre for Basic Sciences, Pt. Ravishankar Shukla University, Raipur CG 492010, India. Electronic address: bgupta1517@gmail.com
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$a Ghosh, Kallol K $u School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur, CG 492010, India
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$a Tripathi, Rama P $u National Institute of Pharmaceutical Education and Research-Raebareli, Sarojini Nagar, Lucknow, Uttar Pradesh 226301, India
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$a Musilek, Kamil $u University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, Hradec Kralove, Czech Republic
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$a Kuca, Kamil $u University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, Hradec Kralove, Czech Republic; University Hospital, Biomedical Research Center, Sokolska 581, 50005, Hradec Kralove, Czech Republic. Electronic address: kamil.kuca@uhk.cz
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