ISSN 1214-0287 (on-line), ISSN 1214-021X (printed)
J Appl Biomed
Volume 9 (2011) No 3, p 163-171
DOI 10.2478/v10136-009-0037-1

Docking studies and effects of syn-anti isomery of oximes derived from pyridine imidazol bicycled systems as potential human acetylcholinesterase reactivators

Ana Paula Guimaraes, Tanos Celmar Costa Franca, Teodorico Castro Ramalho, Magdalena Nascimento Renno, Elaine Fontes Ferreira da Cunha, Karina Silvia Matos, Daiana Teixeira Mancini, Kamil Kuca

Address: Teodorico Castro Ramalho, Chemistry Department - Federal University of Lavras - Campus Universitario, 3037, 37200-000, Lavras, MG, Brazil
teo@dqi.ufla.br

Received 15th November 2010.
Revised 10th February 2011.
Published online 7th April 2011.

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SUMMARY
In order to contribute to a better understanding of the mechanism of action of oximes, we evaluated the affinities of 10 new oximes, derived from pyridine-imidazol bicycled systems, for human acetylcholinesterase (HssAChE) complexed with tabun, by estimating their docking energy values and comparing of the values obtained to known oximes using the software Molegro Virtual Docker (MVD)®. We evaluated the influence of the position of the oxime group as substituent in the structures and, also, the influence of the oxime group syn-anti isomery on the docking score values for all the molecules studied. Results suggest that: the affinities of the 10 new oximes for the tabun inhibited HssAChE active site are better than pralidoxime’s and similar to trimedoxime’s; the meta-pralidoxime could have more affinity for the HssAChE active site and the oximes’ anti isomers could present slightly better affinities for the HssAChE active site than the syn isomers.

KEY WORDS
acetylcholinesterase; docking studies; oximes; neurotoxic agents; theoretical calculation

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