TY - JOUR
T1 - Voltage-dependent sodium channel blocker anticonvulsants
T2 - An approach to the structure-activity relationship
AU - Salazar-López, María Del Carmen
AU - Guevara-Salazar, Juan Alberto
AU - Arellano-Mendoza, Mónica Griselda
AU - Jiménez-Vázquez, Hugo Alejandro
AU - Benavides, Adriana
AU - Quintana-Zavala, Delia
N1 - Publisher Copyright:
© 2021 Bentham Science Publishers.
PY - 2021
Y1 - 2021
N2 - 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, voltage-dependent 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 bioiso-steric 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.
AB - 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, voltage-dependent 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 bioiso-steric 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.
KW - IC
KW - Pharmacophore
KW - QSAR
KW - SAR
KW - SAnticonvulsants
KW - Voltage-gated sodium channel blockers
UR - http://www.scopus.com/inward/record.url?scp=85119876265&partnerID=8YFLogxK
U2 - 10.2174/1573406416666200930113511
DO - 10.2174/1573406416666200930113511
M3 - Artículo
C2 - 32998678
AN - SCOPUS:85119876265
SN - 1573-4064
VL - 17
SP - 1023
EP - 1045
JO - Medicinal Chemistry
JF - Medicinal Chemistry
IS - 9
ER -