Polypharmacological drug design opportunities against Parkinson's disease
Por:
Garcia-Romero E.M., López-López E., Soriano-Correa C., Medina-Franco J.L., Barrientos-Salcedo C.
Publicada:
1 ene 2022
Resumen:
Background: Parkinson's disease is an attractive disease model to extend research towards a better understanding of the interrelationship between genes and the environment (exposome) therefore is an ideal model for a polypharmacological approach due to its clinical heterogeneity. Methods: In this paper, we present a series of polypharmacological chemical scaffolds extracted from ChEMBL 30 Database, with two or more targets of PD-related proteins obtained through chemoinformatics methods. This way, we describe the first adaptation of the Dual Activity Difference (DAD) map that allows the direct identification of "dual activity cliffs". Results: We identified 25 antiparkinson small molecules whose pharmacological targets are directed to dopaminergic and muscarinic acetyl choline M1-M5 receptors; 2 small molecules with three pharmacological targets with norepinephrine transporter, dopaminergic D1-D2 and muscarinic acetyl choline M1-M5 receptors; 6 with both targets norepinephrine transporter and muscarinic acetyl choline M1-M5 receptors; 2 small molecules with norepinephrine transporter and muscarinic acetyl choline M1-M5 receptors and 1 with both adenosine A2a and Dopamine D1-D5 receptors. Conclusion: Chemoinformatics methods identified 36 polypharmacological chemical scaffolds related to Parkinson's disease. Demonstrating that the design of polypharmacological drugs is an opportunity in PD. Copyright: © 2022 Garcia-Romero EM et al.
Filiaciones:
Garcia-Romero E.M.:
Doctorado en Investigaciones Cerebrales, Brain Research Institute, Universidad Veracruzana, Veracruz, Xalapa, 91190, Mexico
López-López E.:
Department of Chemistry and Graduate Program in Pharmacology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico, Mexico City, 07360, Mexico
Soriano-Correa C.:
Computational Chemistry Area, Facultad de Estudios superiores Zaragoza, Universidad Nacional Autónoma de México, Mexico City, 09230, Mexico
Medina-Franco J.L.:
DIFACQUIM Research Group, Department of Pharmacy, School of Chemistry, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Barrientos-Salcedo C.:
Bioanalysis College, Medicinal and Chemogenomics Laboratory, Universidad Veracruzana, Veracruz, Veracruz, 91700, Mexico
All Open Access; Gold
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