Rational Design, In Silico studies, Synthesis, and Biological Evaluation of Azetidine-Based Compounds for Antidiabetic Activity
Abstract
Diabetes mellitus remains a significant global health concern, necessitating the discovery of novel therapeutic agents
with improved efficacy and safety profiles. The present study focused on the design and evaluation of azetidine
derivatives as potential antidiabetic agents. A total of 40 azetidine derivatives were designed and screened using in-silico
tools to assess their physicochemical and pharmacokinetic properties. Molecular docking was performed against the
target protein DPP4 (PDB ID: 5Y7J) to evaluate their binding affinity, using metformin as the reference standard.
Compounds F40, F33, F07, F21, and F39 showed enhanced binding interactions, with F40 exhibiting the most favourable
binding energy (–8.56409 kcal/mol). The top-performing candidates were synthesized via cyclization of Schiff bases
using chloroacetyl chloride, and their structures were confirmed through IR, NMR, and mass spectrometry. In vivo
antidiabetic studies demonstrated that compound F40 significantly improved glycemic control and lipid profile
parameters in treated animals, without observable toxicity at doses up to 1000 mg/kg. Our study reveals that azetidine
pharmacophore are one of the important pharmacophores to develop antidiabetic potential compounds.
How strong is the evidence?
Evidence Hub reads this as a simulation / modelling, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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