Design, synthesis, in silico , and in vitro evaluation of benzylbenzimidazolone derivatives as potential drugs on α-glucosidase and glucokinase as pharmacological targets.

Autor:	Santos-Ballardo CL; Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa México ulises.osuna@uas.edu.mx jmontes@uas.edu.mx., Montes-Ávila J; Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa México ulises.osuna@uas.edu.mx jmontes@uas.edu.mx., Rendon-Maldonado JG; Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa México ulises.osuna@uas.edu.mx jmontes@uas.edu.mx., Ramos-Payan R; Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa México ulises.osuna@uas.edu.mx jmontes@uas.edu.mx., Montaño S; Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa México ulises.osuna@uas.edu.mx jmontes@uas.edu.mx., Sarmiento-Sánchez JI; Facultad de Ingeniería Civil, Universidad Autónoma de Sinaloa México., Acosta-Cota SJ; Departamento de Ciencias de la Salud, Universidad Autónoma de Occidente México., Ochoa-Terán A; Centro de Graduados e Investigación en Química, Instituto Tecnológico de Tijuana México., Bastidas-Bastidas PJ; Laboratorio de Análisis de Residuos de Plaguicidas, Centro de Investigación en Alimentación y Desarrollo A.C. México., Osuna-Martínez U; Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa México ulises.osuna@uas.edu.mx jmontes@uas.edu.mx.
Jazyk:	angličtina
Zdroj:	RSC advances [RSC Adv] 2023 Jul 12; Vol. 13 (31), pp. 21153-21162. Date of Electronic Publication: 2023 Jul 12 (Print Publication: 2023).
DOI:	10.1039/d3ra02916f
Abstrakt:	Benzimidazolones have shown biological activities, including antihyperglycemic and hypoglycemic, by inhibiting or activating of α-glu and GK. The aim of this study is the rational design of compounds using in silico assays to delimitate the selection of structures to synthesize and the in vitro evaluation of benzimidazolone derivatives in blood glucose control. A docking of 23 benzimidazolone derivatives was performed; selecting the compounds with better in silico profiles to synthesize by microwave-irradiation/conventional heat and evaluate in enzymatic in vitro evaluation. Compounds 2k, 2m, 2r, and 2s presented the best in silico profiles, showing good affinity energy (-10.9 to -8.6 kcal mol -1 ) and binding with catalytic-amino acids. They were synthesized at 70 °C and 24 h using DMF as the solvent and potassium carbonate (yield: 22-38%). The results with α-glu showed moderate inhibition of 2k (14 ± 1.23-29 ± 0.45), 2m (12 ± 2.21-36 ± 0.30), 2r (7 ± 2.21-13 ± 1.34), and 2s (11 ± 0.74-35 ± 2.95) at evaluated concentrations (0.1 to 100 μg mL -1 ). The GK activation assay showed an enzymatic activity increase; compound 2k increased 1.31 and 2.83 more than normal activity, 2m (2.13-fold), 2s (2.86 and 3.74-fold) at 100 and 200 μg mL -1 respectively. The present study showed that the 2s derivative presents moderate potential as an α-glu inhibitor and a good activator potential of GK, suggesting that this compound is a good candidate for blood glucose control through antihyperglycemic and hypoglycemic mechanisms. Competing Interests: The authors have no potential conflicts of interest to report. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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