VII Simposio Internacional de Química 2019 "SIQ 2019" -VII Conferencia "Ciencias Químicas"

VII Simposio Internacional de Química 2019

SIQ 2019

MOLECULAR DOCKING STUDIES OF ARYLSUBSTITUTED IMIDAZOLES AND THE ONCOGENIC PROTEIN BCR-ABL TYROSINE KINASE.

Resumen [ES]

The treatment of chronic myeloid leukemia (CML) should be considered one of the medical successes of the last 30 years. CML is a myeloproliferative disorder that seriously compromises the health and lifestyle of the patient who suffers. If not detected in time, the evolution of it can lead to a fatal end. The Philadelphia Chromosome (CrPh) is present in approximately 95% of patients with CML, constituting a diagnostic marker of the disease. It is formed by the Bcr-Abl oncogene. In the present work it was carried out a molecular docking study between 12 arylsubstituted imidazoles and two oncogene protein Bcr-Abl, Abl kinase (3CS9) and T315I mutation (2V7A). To carry out the molecular docking, the Autodock 4.2 program was used, while the crystalline structures of the proteins were extracted from the Protein Data Bank database. A docking study was also carried out with co-crystalized substrates in each protein and a set of drugs currently used against CML. According to the results obtained, imidazoles 5a, 5d and 5j have a greater affinity towards the Abl kinase, whereas 5e, 5g and 5i towards the T315I mutation. In addition, these imidazoles were found to have better couplings than the substrates and drugs studied, only surpassed by Dasatinib and Ponatinib.

Resumen [EN]

The treatment of chronic myeloid leukemia (CML) should be considered one of the medical successes of the last 30 years. CML is a myeloproliferative disorder that seriously compromises the health and lifestyle of the patient who suffers. If not detected in time, the evolution of it can lead to a fatal end. The Philadelphia Chromosome (CrPh) is present in approximately 95% of patients with CML, constituting a diagnostic marker of the disease. It is formed by the Bcr-Abl oncogene. In the present work it was carried out a molecular docking study between 12 arylsubstituted imidazoles and two oncogene protein Bcr-Abl, Abl kinase (3CS9) and T315I mutation (2V7A). To carry out the molecular docking, the Autodock 4.2 program was used, while the crystalline structures of the proteins were extracted from the Protein Data Bank database. A docking study was also carried out with co-crystalized substrates in each protein and a set of drugs currently used against CML. According to the results obtained, imidazoles 5a, 5d and 5j have a greater affinity towards the Abl kinase, whereas 5e, 5g and 5i towards the T315I mutation. In addition, these imidazoles were found to have better couplings than the substrates and drugs studied, only surpassed by Dasatinib and Ponatinib.

Sobre el ponente

Julio Rojas Vargas

MsC. Julio Rojas Vargas

UO Flag of Cuba
Información Práctica
English (US)
No definido
30 minutos
No definido
Autores
Prof. Phd Matheus Froeyen
Est. Lianne Álvarez Rodríguez
MsC. Julio Rojas Vargas
Phd América García López
Palabras clave
aryl-substituted imidazoles
chronic myeloid leukemia (cml)
molecular docking
protein bcr-abl