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- Title
NEAR ATTACK CONFORMATION APPROACH FOR MOLECULAR MODELING STUDIES UPON THE PROPHYLACTIC AGENT 7-METHOXYTACRINE-4-PYRIDINEALDOXIME HYBRID COMPARED WITH OTHER REACTIVATORS OF VX-INHIBITED HssAChE.
- Authors
da Silva, Jorge Alberto Valle; Nepovimova, Eugenie; Kuča, Kamil; Ramalho, Teodorico Castro; França, Tanos Celmar Costa
- Abstract
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.
- Subjects
CONDOMS; ACETYLCHOLINESTERASE inhibitors; MOLECULAR dynamics; ALDOXIMES; MOLECULAR docking
- Publication
Military Medical Science Letters / Vojenské zdravotnické Listy, 2018, Vol 87, p99
- ISSN
0372-7025
- Publication type
Article