NEAR ATTACK CONFORMATION APPROACH FOR MOLECULAR MODELING STUDIES UPON THE PROPHYLACTIC AGENT 7-METHOXYTACRINE-4-PYRIDINEALDOXIME HYBRID COMPARED WITH OTHER REACTIVATORS OF VX-INHIBITED HssAChEMeeting abstracts
- Jorge Alberto Valle da Silva1, Eugenie Nepovimova2, Kamil Kuča
ORCID...3, Teodorico Castro Ramalho3,4, Tanos Celmar Costa Franįa1,3 - 1 Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro/RJ, Brazil
- 2 Biomedical Research Centre, University Hospital Hradec Kralove, Czech Republic
- 3 Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic
- 4 Laboratory of Molecular Modeling, Chemistry Department, Federal University of Lavras, Lavras, MG, Brazil
The novel 7-methoxytacrine-4-pyridinealdoxime agent, named hybrid 5C, is a hybrid compound comprised of a linkage between 7-methoxytacrine (7-MEOTA-4-PA) and reactivator 4-pyridinealdoxime (4-PA) moieties through a 5-carbon length-spacer. This compound was formerly designed as a prophylactic agent for intoxication by organophosphates (OP), able to form a complex with acetylcholinesterase (AChE) and reactivate this enzyme in case of OP inhibition. In order to check if the 5 carbons spacer is the ideal to maximize the interactions of this compound inside AChE, we performed in this work docking, molecular dynamics and mmpbsa studies on a series of analogues of hybrid 5C, varying the spacer-length from 1 to 10 carbons long. Our results helped to elucidate the interactions of these compounds with the different binding sites inside human AChE (HssAChE) and pointed to the 4 and 5 carbons long as the best spacers for optimizing these interactions.
Keywords: Acetylcholinesterase; molecular modeling; aldoxime; 7-MEOTA-4-PA
Published: September 2, 2018 Show citation
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