Título:	Unraveling the Antihyperglycemic Effects of Dipeptyl Peptidase-4 Inhibitors in Rodents: A Multi-Faceted Approach Combining Effects on Glucose Homeostasis, Molecular Docking, and ADMET Profiling.
Autoria:	RORIZ, R. N. S. CARDOZO, C. J. P. FREIRE, G. A. MARTINS, C. B. R. XAVIER FILHO, R. R. B. PEREIRA, L. L. RANGEL, G. F. P. SAMPAIO, T. L. RIBEIRO, L. R. SILVA, G. S. MAIA, I. WONG, D. V. T. SOUSA, D. O. B. OLIVEIRA, A. C. DE REINA, E. LIMA, L. M. PELÁEZ, W. ROCHA, M. N. DA MARINHO, M. M. SANTOS, H. S. DOS MARINHO, E. S. MENEZES, J. E. S. A. DE SILVA, F. R. M. B. CANUTO, K. M. ALENCAR, N. M. N. FREDERICO, M. J. S.
Afiliação:	RAQUEL N. S. RORIZ, UNIVERSIDADE FEDERAL DO CEARÁ; CLAUDIA J. P. CARDOZO, UNIVERSIDADE FEDERAL DO CEARÁ; GABRIELA A. FREIRE, UNIVERSIDADE FEDERAL DO CEARÁ; CAIO B. R. MARTINS, UNIVERSIDADE FEDERAL DO CEARÁ; RAIMUNDO RIGOBERTO B. XAVIER FILHO, UNIVERSIDADE ESTADUAL DO CEARÁ; LANDERSON LOPES PEREIRA, UNIVERSIDADE FEDERAL DO CEARÁ; GISELE F. P. RANGEL, UNIVERSIDADE FEDERAL DO CEARÁ; TIAGO L. SAMPAIO, UNIVERSIDADE FEDERAL DO CEARÁ; LYANNA R. RIBEIRO, UNIVERSIDADE FEDERAL DO CEARÁ; GISELE SILVESTRE SILVA, UNIVERSIDADE FEDERAL DO CEARÁ; ISABELLE MAIA, UNIVERSIDADE FEDERAL DO CEARÁ; DEYSI VIVIANA TENAZOA WONG, UNIVERSIDADE FEDERAL DO CEARÁ; DANIELE O. B. SOUSA, UNIVERSIDADE FEDERAL DO CEARÁ; ARICLÉCIO CUNHA DE OLIVEIRA, UNIVERSIDADE ESTADUAL DO CEARÁ; EDUARDO REINA, UNIVERSIDADE FEDERAL DO RIO DE JANEIRO; LIDIA MOREIRA LIMA, UNIVERSIDADE FEDERAL DO RIO DE JANEIRO; WALTER PELÁEZ, CONSEJO NACIONAL DE INVESTIGACIONES CIENTÍFI CAS Y TÉCNICAS; MATHEUS NUNES DA ROCHA, UNIVERSIDADE ESTADUAL DO CEARÁ; MÁRCIA MACHADO MARINHO, UNIVERSIDADE ESTADUAL DO CEARÁ; HÉLCIO SILVA DOS SANTOS, UNIVERSIDADE ESTADUAL DO CEARÁ; EMMANUEL SILVA MARINHO, UNIVERSIDADE ESTADUAL DO CEARÁ; JANE EIRE SILVA ALENCAR DE MENEZES, UNIVERSIDADE ESTADUAL DO CEARÁ; FÁTIMA REGINA MENA BARRETO SILVA, UNIVERSIDADE FEDERAL DE SANTA CATARINA; KIRLEY MARQUES CANUTO, CNPAT; NYLANE M. N. ALENCAR, UNIVERSIDADE FEDERAL DO CEARÁ; MARISA JADNA SILVA FREDERICO, UNIVERSIDADE FEDERAL DO CEARÁ.
Ano de publicação:	2025
Referência:	Pharmaceuticals, 18, 1589, 2025.
Conteúdo:	Background/Objectives: Dipeptidyl peptidase-4 (DPP-4) inhibitors are antidiabetic agents that regulate blood glucose by preventing the degradation of active incretin hormones. Although clinically effective, this drug class is associated with adverse effects, creating the need for new molecular scaffolds with improved safety and effi cacy. Methods: We evalu- ated the antihyperglycemic activity of β-aminohydrazine and β-amino-N-acylhydrazone derivatives (LASSBio-2123, 2125, 2129, and 2130) using a combined in vivo and in silico ap- proach. Male C57BL/6 mice underwent glucose tolerance tests (GTT) and dexamethasoneinduced insulin resistance protocols. Hepatic and skeletal muscle glycogen levels, as well as GLUT4 mRNA expression, were quantifi ed. In silico studies included ADMET predictions and molecular docking analyses against aldose reductase and glucokinase enzymes. MTT was performed on the pancreatic cell line MIN6 (Mus musculus). Results: Among the compounds tested, LASSBio-2129 demonstrated the most promising profi le, with favorable ADMET parameters, metabolic stability, and high docking affi nity for aldose reductase and glucokinase. In vivo, LASSBio-2129 (10 mg/kg, i.p.) reduced blood glucose, increased hep- atic and muscle glycogen storage, and upregulated GLUT4 mRNA expression in skeletal muscle. Additionally, LASSBio-2129 improved insulin sensitivity in the dexamethasone- induced insulin resistance model, with effects comparable to sitagliptin. Conclusions: The combined pharmacological, docking, and ADMET analyses identifi ed LASSBio-2129 as aldose reductase inhibitor candidate and glucokinase activator. Its ability to improve glucose tolerance, enhance glycogen storage, and increase GLUT4 expression highlights its potential as a promising molecule for the treatment of type 2 diabetes mellitus.
NAL Thesaurus:	Insulin resistance Glucokinase
Palavras-chave:	Dipeptyl peptidase-4 inhibitors Aldose reductase
Digital Object Identifier:	https://doi.org/ 10.3390/ph18101589
Tipo do material:	Artigo de periódico
Acesso:	openAccess
Aparece nas coleções:	Artigo em periódico indexado (CNPAT)