Title:Voltage-Dependent Sodium Channel Blocker Anticonvulsants: An Approach to the Structure-Activity Relationship
Volume: 17
Issue: 9
Author(s): María del Carmen Salazar-López, Juan Alberto Guevara-Salazar*, Mónica Griselda Arellano-Mendoza, Hugo Alejandro Jiménez-Vázquez, Adriana Benavides and Delia Quintana-Zavala
Affiliation:
- Departamento de Farmacologia. Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Diaz Miron, S/N, 11340, Mexico, D.F.,Mexico
Keywords:
Anticonvulsants, voltage-gated sodium channel blockers, SAR, QSAR, IC50, pharmacophore.
Abstract:
Background: Anticonvulsants are drugs used in the treatment of seizures; their pharmacology
includes promoters of brain inhibition and inhibitors of brain activity. Of the latter, voltagedependent
sodium channel blockers (VGSCB) are the most widely used in therapeutics.
Objective: The study aimed at proposing the structural requirements of VGSC blockers through a
quantitative structure-activity relationship analysis of drugs with proven activity.
Methods: IC50 values of anticonvulsant drugs on VGSCs were considered under similar experimental
conditions; some physicochemical properties of the molecules that were correlated with their biological
activity were determined in silico.
Results: Relationships were observed between the dipole moment, pKa, EHOMO, and MR with the
biological activity, which infers that between greater polarity and basicity of the drugs, their activity
as blockers will increase. Subsequently, the structural subclassification of the drugs was carried out,
based on the urea derivation, the groups of which were: Group 1 (direct and bioisostere derivatives)
and Group 2 (homologue and vinylogue derivatives of urea).
Conclusion: The biological activity depends on the polarity, basicity, and electronic density of the
drugs. The derivation of urea is essential, which is present in its original substituted form or a bioisosteric
form. Urea can be in the form of a homologue or a vinylogue at the ends of the molecule. Aromatic
substitution to the urea portion is necessary.