Title:	LASSBio-1986 as a multifunctional antidiabetic lead: SGLT1/2 docking, redox–inflammatory modulation and metabolic benefits in C57BL/6 mice.
Authors:	PEREIRA, L. L. XAVIER FILHO, R. R. B. FREIRE, G. A. MARTINS, C. B. R. PEROTE, M. G. B. CAMPOS, C. L. M. MONTEIRO, M. C. S. MAIA, I. de F. V. C. LACERDA, R. B. GELVES, L. G. V. SOUSA, D. S. de SOUZA, R. K. B. de NUNES, P. I. G. SAMPAIO, T. L. SILVA, G. S. WONG, D. V. T. LIMA, L. M. PELÁEZ, W. J. MARINHO, M. M. SANTOS, H. S. dos MENEZES, J. E. S. A. de MARINHO, E. S. CANUTO, K. M. SOUZA, P. F. N. MORAIS, F. S. ALENCAR, N. M. N. de FREDERICO, M. J. S.
Affiliation:	LANDERSON LOPES PEREIRA, UNIVERSIDADE FEDERAL DO CEARÁ; RAIMUNDO RIGOBERTO B. XAVIER FILHO, UNIVERSIDADE ESTADUAL DO CEARÁ; GABRIELA ARAÚJO FREIRE, UNIVERSIDADE FEDERAL DO CEARÁ; CAIO BRUNO RODRIGUES MARTINS, UNIVERSIDADE FEDERAL DO CEARÁ; MAURÍCIO GABRIEL BARROS PEROTE, UNIVERSIDADE FEDERAL DO CEARÁ; CIBELLY LORYN MARTINS CAMPOS, UNIVERSIDADE FEDERAL DO CEARÁ; MANUEL CARLOS SERRAZUL MONTEIRO, UNIVERSIDADE FEDERAL DO CEARÁ; ISABELLE DE FÁTIMA VIEIRA CAMELO MAIA, UNIVERSIDADE FEDERAL DO CEARÁ; RENATA BARBOSA LACERDA, UNIVERSIDADE FEDERAL RURAL DO RIO DE JANEIRO; LUIS GABRIEL VALDIVIESO GELVES, UNIVERSIDADE FEDERAL DO RIO DE JANEIRO; DAMIÃO SAMPAIO DE SOUSA, UNIVERSIDADE ESTADUAL DO CEARÁ; RÉGIA KAREN BARBOSA DE SOUZA, UNIVERSIDADE FEDERAL DO CEARÁ; PAULO IURY GOMES NUNES, UNIVERSIDADE FEDERAL DO CEARÁ; TIAGO LIMA SAMPAIO, UNIVERSIDADE FEDERAL DO CEARÁ; GISELE SILVESTRE SILVA, UNIVERSIDADE FEDERAL DO CEARÁ; DEYSI VIVIANA TENAZOA WONG, UNIVERSIDADE FEDERAL DO CEARÁ; LIDIA MOREIRA LIMA, UNIVERSIDADE FEDERAL DO RIO DE JANEIRO; WALTER JOSÉ PELÁEZ, INSTITUTO DE INVESTIGACIONES EN FÍSICO-QUÍMICA DE CÓRDOBA; MÁRCIA MACHADO MARINHO, UNIVERSIDADE ESTADUAL DO CEARÁ; HÉLCIO SILVA DOS SANTOS, UNIVERSIDADE ESTADUAL DO CEARÁ; JANE EIRE SILVA ALENCAR DE MENEZES, UNIVERSIDADE ESTADUAL DO CEARÁ; EMMANUEL SILVA MARINHO, UNIVERSIDADE ESTADUAL DO CEARÁ; KIRLEY MARQUES CANUTO, CNPAT; PEDRO FILHO NORONHA SOUZA, UNIVERSIDADE FEDERAL DO CEARÁ; FRANCIMAURO SOUSA MORAIS, INSTITUTO FEDERAL DE EDUCAÇÃO, CIÊNCIA E TECNOLOGIA DO AMAZONAS; NYLANE MARIA NUNES DE ALENCAR, UNIVERSIDADE FEDERAL DO CEARÁ; MARISA JADNA SILVA FREDERICO, UNIVERSIDADE FEDERAL DO CEARÁ.
Date Issued:	2026
Citation:	International Journal of Molecular Sciences, v. 27, n. 2, 829, Jan. 2026.
Description:	Type 2 diabetes mellitus (T2DM) involves chronic hyperglycemia, insulin resistance, low-grade inflammation, and oxidative stress that drive cardiometabolic and renal damage despite current therapies. Sodium–glucose cotransporter (SGLT) inhibitors have reshaped the treatment landscape, but residual risk and safety concerns highlight the need for new agents that combine glucose-lowering efficacy with redox–inflammatory modulation. LASSBio-1986 is a synthetic N-acylhydrazone (NAH) derivative designed as a gliflozin-like scaffold with the potential to interact with SGLT1/2 while also influencing oxidative and inflammatory pathways. Here, we integrated in silico and in vivo approaches to characterize LASSBio-1986 as a multifunctional antidiabetic lead in murine models of glucose dysregulation. PASS and target class prediction suggested a broad activity spectrum and highlighted transporter- and stress-related pathways. Molecular docking indicated high-affinity binding to both SGLT1 and SGLT2, with a modest energetic preference for SGLT2, and ADME/Tox predictions supported favorable oral drug-likeness. In vivo, intraperitoneal LASSBio-1986 improved oral glucose tolerance and reduced glycemic excursions in an acute glucose challenge model in C57BL/6 mice, while enhancing hepatic and skeletal muscle glycogen stores. In a dexamethasone-induced insulin-resistance model, LASSBio-1986 improved insulin sensitivity, favorably modulated serum lipids, attenuated thiobarbituric acid-reactive substances (TBARS), restored reduced glutathione (GSH) levels, and rebalanced pro- and anti-inflammatory cytokines in metabolic tissues, with efficacy broadly comparable to dapagliflozin. These convergent findings support LASSBio-1986 as a preclinical, multimodal lead that targets SGLT-dependent glucose handling while mitigating oxidative and inflammatory stress in models relevant to T2DM. Chronic disease models, formal toxicology, and pharmacokinetic studies, particularly with oral dosing, will be essential to define its translational potential.
NAL Thesaurus:	Insulin resistance Oxidative stress Cytokines Diabetes mellitus
Keywords:	N-acylhydrazone SGLT1 SGLT2 Glucose metabolism GLUT-4 expression Molecular docking Type 2 diabetes mellitus N-acil-hidrazona Metabolismo da glicose Resistência à insulina Expressão de GLUT-4 Estresse oxidativo Citocinas Acoplamento molecular Diabetes mellitus tipo 2
ISSN:	1422-0067
DOI:	https://doi.org/10.3390/ijms27020829
Type of Material:	Artigo de periódico
Access:	openAccess
Appears in Collections:	Artigo em periódico indexado (CNPAT)