ArticleMolecular and cellular biochemistry2026
Potential of imidazole derivatives in reducing vascular complications in experimental diabetes.
Article in Molecular and cellular biochemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Diabetes-induced endothelial dysfunction significantly contributes to cardiovascular complications, yet there is a limited availability of effective targeted therapies. This study assessed two novel imidazole derivatives, DMB-PTCI and ADBPI, through an integrated multiscale approach that includes quantum chemical analysis, in vivo validation, and computational modelling. Density functional theory revealed that DMB-PTCI exhibits a narrower HOMO-LUMO gap (2.96 vs. 3.91 eV), higher electrophilicity (1.88 vs. 1.25 eV), and greater softness (0.18 vs. 0.16 eV⁻¹) compared to ADBPI, indicating enhanced reactivity. In streptozotocin-induced diabetic rats, DMB-PTCI and ADBPI significantly reduced fasting blood glucose levels from 285.0 ± 15.5 mg/dL to 121.2 ± 6.7 mg/dL and 148.7 ± 6.5 mg/dL, respectively. Additionally, these treatments restored insulin levels from 3.9 ± 0.4 µIU/mL to 9.9 ± 0.4 µIU/mL and 9.2 ± 0.3 µIU/mL. Both compounds demonstrated improvements in lipid profiles, oxidative stress, inflammation, and endothelial biomarkers. Notably, DMB-PTCI exhibited stronger effects, as indicated by lower malondialdehyde levels (53.3 ± 1.9 nmol/g tissue) and higher nitric oxide levels (28.7 ± 0.7 nmol/g tissue). Molecular docking studies on human lysosomal acid-α-glucosidase revealed that DMB-PTCI binds more strongly (-8.455 kcal/mol) than ADBPI (-7.590 kcal/mol) and the reference ligand (-5.102 kcal/mol). This finding is further supported by MM-PBSA binding free energy calculations, which yielded a value of -11.60 ± 8.66 kcal/mol. Additionally, ADMET analysis indicated a prolonged half-life for DMB-PTCI (108.60 h), while ADBPI demonstrated higher oral bioavailability (0.97). Overall, DMB-PTCI consistently demonstrated superior performance across theoretical, experimental, and computational evaluations. This highlights its potential as a leading candidate for managing diabetes-associated endothelial dysfunction and suggests the need for further preclinical investigation.ADMET profiling revealed safety concerns, including the risk of hepatotoxicity and poor solubility associated with DMB-PTCI, indicating the need for further structural optimization and preclinical validation prior to clinical translation.
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