Molecular Docking Studies on Anticonvulsant Enaminones Inhibiting Voltage-Gated Sodium Channels
Open Access
- 1 January 2019
- journal article
- research article
- Published by Scientific Research Publishing, Inc. in Open Journal of Physical Chemistry
- Vol. 09 (04), 241-257
- https://doi.org/10.4236/ojpc.2019.94015
Abstract
Epilepsy is described as the most common chronic brain disorder. A typical symptom of epilepsy results in uncontrolled convulsions caused by temporary excessive neuronal discharges. Although several new anticon-vulsants have been introduced, some types of seizures have still not been adequately controlled with these new and current therapies. There is an urgent need to develop new anticonvulsant drugs to control the many different types of seizures. Many studies have shown that the epilepsies involve more than one mechanism and therefore may be responsible for the various types of observed seizures. Recently reported studies have shown that a group of newly synthesized 6 Hz active anticonvulsant fluorinated N-benzamide enaminones exhibited selective inhibitions of voltage-gated sodium (Nav) channels. Nav channels are responsible for the initial inward currents during the depolarization phases of the action potential in excitable cells. The activation and opening of Nav channels result in the initial phases of action potentials. We hypothesize that there is an essential pharmacophore model for the interactions between these enaminones and the active sites of Nav channels. The research reported here is focused on molecular docking studies of the interactions that occur between the fluorinated N-benzamide enaminones and the Nav channels. These studies may open an avenue for designing anticonvulsant drugs by inhibiting Nav channels.Keywords
This publication has 17 references indexed in Scilit:
- 6 Hz Active Anticonvulsant Fluorinated N-Benzamide Enaminones and Their Inhibitory Neuronal ActivityInternational Journal of Environmental Research and Public Health, 2018
- The complete structure of an activated open sodium channelNature Communications, 2017
- Novel drug design for Chagas disease via targeting Trypanosoma cruzi tubulin: Homology modeling and binding pocket prediction on Trypanosoma cruzi tubulin polymerization inhibition by naphthoquinone derivativesBioorganic & Medicinal Chemistry, 2016
- Allosteric Modulation of GABAA Receptors by an Anilino Enaminone in an Olfactory Center of the Mouse BrainPharmaceuticals, 2014
- Enaminones 11. An examination of some ethyl ester enaminone derivatives as anticonvulsant agentsBioorganic & Medicinal Chemistry, 2013
- Enaminones 12. An explanation of anticonvulsant activity and toxicity per Linus Pauling’s clathrate hypothesisEuropean Journal of Medicinal Chemistry, 2012
- Enaminones 8: CoMFA and CoMSIA studies on some anticonvulsant enaminonesBioorganic & Medicinal Chemistry, 2009
- Newer GABA derivatives for the treatment of epilepsy including febrile seizures: A bioisosteric approachEuropean Journal of Medicinal Chemistry, 2008
- Enaminones: Exploring Additional Therapeutic ActivitiesJournal of Pharmaceutical Sciences, 2007
- Medicinal Chemistry of Neuronal Voltage-Gated Sodium Channel BlockersJournal of Medicinal Chemistry, 2001