LASSBio-1986 as a Multifunctional Antidiabetic Lead: SGLT1/2 Docking, Redox-Inflammatory Modulation and Metabolic...

Area of Science:

• Pharmacology and Drug Discovery
• Metabolic Diseases
• Oxidative Stress and Inflammation

Background:

• Type 2 diabetes mellitus (T2DM) involves hyperglycemia, insulin resistance, inflammation, and oxidative stress, leading to organ damage.
• Current therapies like SGLT inhibitors offer benefits but leave residual risks, necessitating novel agents with combined glucose-lowering and redox-inflammatory modulation.

Purpose of the Study:

• To characterize LASSBio-1986, a synthetic N-acylhydrazone derivative, as a multifunctional antidiabetic lead.
• To evaluate its potential to interact with SGLT1/2 and modulate oxidative and inflammatory pathways.

Main Methods:

• Integrated in silico (PASS, molecular docking, ADME/Tox) and in vivo approaches in murine models.
• Assessed oral glucose tolerance, glycemic excursions, insulin sensitivity, lipid profiles, oxidative stress markers (TBARS, GSH), and cytokine balance.

Main Results:

• In silico analysis predicted broad activity, high affinity for SGLT1/2, and favorable oral drug-likeness.
• In vivo studies demonstrated improved glucose tolerance, enhanced glycogen stores, better insulin sensitivity, and modulated lipid and redox-inflammatory profiles.
• LASSBio-1986 showed efficacy comparable to dapagliflozin in relevant T2DM models.

Conclusions:

• LASSBio-1986 is a promising preclinical, multimodal antidiabetic lead targeting SGLT and mitigating oxidative/inflammatory stress.
• Further research, including chronic disease models, toxicology, and oral pharmacokinetic studies, is crucial for its translational potential.