Convergent synthesis, drug target prediction, and docking studies of new 2,6,9-trisubstituted purine derivatives

Primer Autor
Salas, Cristian O.
Co-autores
Villegas, Alondra
Satheeshkumar, Rajendran
Ballesteros-Casallas, Andres
Paulino, Margot
Castro, Alejandro
Espinosa-Bustos, Christian
Título
Convergent synthesis, drug target prediction, and docking studies of new 2,6,9-trisubstituted purine derivatives
Editorial
WILEY
Revista
JOURNAL OF HETEROCYCLIC CHEMISTRY
Lenguaje
en
Resumen
A set of new 2,6,9-trisubstituted purine derivatives were designed and synthesized from 6-chloro-2-fluoro-9-alkyl-9H-purine as the key starting material. These purines were synthesized via a multistep protocol and finally subjected to SNAr with various aminopiperidinyl salts. The structures of these compounds were established by substantiating them through spectral techniques like FT-IR, H-1-NMR, C-13-NMR, and F-19-NMR. In addition, for two purine derivatives, a reverse screening strategy based on ligand similarity (PharmMapper web server) resulted in a set of predicted protein target candidates. Interestingly, for both purines, the main potential target candidates belonged to key proteins involved within signaling pathways that are related to proliferation or survival of cancer cells. These proteins correspond mainly to enzymes and specifically kinases. To check if our purines could be ligands for two kinases involved in cancer, docking studies were performed. The results indicated that these purines fitted in the same cavity of crystalized inhibitors. Therefore, in this work we are developed new purine derivatives that could be good inhibitors of some kinases.
Tipo de Recurso
artículo original
Description
A.V. thanks to CONICYT-PCHA/Doctorado Nacional l/2015-21150586 and C.O.S. thanks to DIPOG project No. 3913-406-81 and Fondequip EQM170172.
AV. gracias a CONICYT-PCHA/Doctorado Nacional l/2015-21150586 y C.O.S. gracias al proyecto DIPOG N° 3913-406-81 y Fondequip EQM170172.
doi
10.1002/jhet.4368
Formato Recurso
PDF
Palabras Claves
SMALL-MOLECULE INHIBITORS
WEB SERVER
PROTEIN
IDENTIFICATION
NUCLEOSIDES
RECEPTORS
SCAFFOLD
POTENT
GLIDE
Ubicación del archivo
http://dx.doi.org/10.1002/jhet.4368
Categoría OCDE
Química Orgánica
Materias
INHIBIDORES DE MOLÉCULAS PEQUEÑAS
SERVIDOR WEB
PROTEÍNAS
IDENTIFICACIÓN
NUCLEOSIDOS
RECEPTORES
SCAFFOLD
POTENTE
GLIDE
Disciplinas de la OCDE
Farmacología y Farmacia
Química Orgánica
Oncología
Título de la cita (Recomendado-único)
Convergent synthesis, drug target prediction, and docking studies of new 2,6,9-trisubstituted purine derivatives
Página de inicio (Recomendado-único)
97
Página final (Recomendado-único)
111
Identificador del recurso (Mandatado-único)
artículo original
Versión del recurso (Recomendado-único)
version publicada
Condición de la licencia (Recomendado-repetible)
0
Derechos de acceso
acceso abierto
Access Rights
acceso abierto
Referencia del Financiador (Mandatado si es aplicable-repetible)
ANID-FONDEQUIP EQM170172
CONICYT-PCHA 2015-21150586
ANID FONDEQUIP EQM170172
Id de Web of Science
WOS:000703345800001
Colecciones
Colección Publicaciones Científicas
Colección ANID
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