LASSBio-1986 as a Multifunctional Antidiabetic Lead: SGLT1/2 Docking, Redox–Inflammatory Modulation and Metabolic Benefits in C57BL/6 Mice
Year: 2026
Type: article
Abstract: 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.
DOI: 10.3390/ijms27020829
Authors: Landerson Lopes Pereira, Raimundo Rigoberto B. Xavier Filho, Gabriela Araújo Freire, Caio Bruno Rodrigues Martins, Maurício Gabriel Barros Perote, Cibelly Loryn Martins Campos, Manuel Carlos Serrazul Monteiro, Isabelle de Fátima Vieira Camelo Maia, Renata Barbosa Lacerda, Luis Gabriel Valdivieso Gelves, Damião Sampaio de Sousa, Régia Karen Barbosa De Souza, Paulo Iury Gomes Nunes, Tiago Lima Sampaio, Gisele Silvestre Silva, Deysi Viviana Tenazoa Wong, Lidia Moreira Lima, Walter José Peláez, Márcia Machado Marinho, Hélcio Silva dos Santos, Jane Eire Silva Alencar de Menezes, Emmanuel Silva Marinho, Kirley Marques Canuto, Pedro Filho Noronha Souza, Francimauro Sousa Morais, Nylane Maria Nunes de Alencar, Marisa Jadna Silva Frederico
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7124164877