Multi-target Phenylpropanoids Against Epilepsy

Title:Multi-target Phenylpropanoids Against Epilepsy

Volume: 22 Issue: 13

Author(s): Teresa Carolliny Moreira Lustoza Rodrigues, Arthur Lins Dias, Aline Matilde Ferreira dos Santos, Alex France Messias Monteiro, Mayara Cecile Nascimento Oliveira, Hugo Fernandes Oliveira Pires, Natália Ferreira de Sousa, Mirian Graciela da Silva Stiebbe Salvadori, Marcus Tullius Scotti and Luciana Scotti*

Affiliation:

• Cheminformatics Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba, 58051-900, João Pessoa, Paraíba, Brazil
• Teaching and Research Management, University Hospital Lauro Wanderley, Federal University of Paraíba, 58050-585, João Pessoa, PB, Brazil

Keywords: Epilepsy, phenylpropanoids, multi-target, molecular docking, GABAA, AMPA.

Abstract: Epilepsy is a neurological disease with no defined cause, characterized by recurrent epileptic seizures. These occur due to the dysregulation of excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Psychopharmaceuticals have undesirable side effects; many patients require more than one pharmacotherapy to control crises. With this in mind, this work emphasizes the discovery of new substances from natural products that can combat epileptic seizures. Using in silico techniques, this review aims to evaluate the antiepileptic and multi-target activity of phenylpropanoid derivatives. Initially, ligand-based virtual screening models (LBVS) were performed with 468 phenylpropanoid compounds to predict biological activities. The LBVS were developed for the targets alpha- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), voltage-gated calcium channel Ttype (CaV), gamma-aminobutyric acid A (GABAA), gamma-aminobutyric acid transporter type 1 (GAT-1), voltage-gated potassium channel of the Q family (KCNQ), voltage-gated sodium channel (NaV), and N-methyl D-aspartate (NMDA). The compounds that had good results in the LBVS were analyzed for the absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and later, the best molecules were evaluated in the molecular docking consensus. The TR430 compound showed the best results in pharmacokinetic parameters; its oral absorption was 99.03%, it did not violate any Lipinski rule, it showed good bioavailability, and no cytotoxicity was observed either from the molecule or from the metabolites in the evaluated parameters. TR430 was able to bind with GABAA (activation) and AMPA (inhibition) targets and demonstrated good binding energy and significant interactions with both targets. The studied compound showed to be a promising molecule with a possible multi-target activity in both fundamental pharmacological targets for the treatment of epilepsy.

Cite this article as:

Rodrigues Carolliny Moreira Lustoza Teresa, Dias Lins Arthur, dos Santos Matilde Ferreira Aline, Monteiro France Messias Alex, Oliveira Cecile Nascimento Mayara, Pires Fernandes Oliveira Hugo, de Sousa Ferreira Natália, Salvadori Graciela da Silva Stiebbe Mirian, Scotti Tullius Marcus and Scotti Luciana*, Multi-target Phenylpropanoids Against Epilepsy, Current Neuropharmacology 2024; 22 (13) . https://dx.doi.org/10.2174/1570159X22666240524160126