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Updated: Jun 21, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Functionalized thiazole and thiophene compounds as aldose reductase inhibitors: from rational design to biological
Heba M Metwally1, Mariam M Kiwan2, Bakr F Abdel-Wahab3
1Organic Chemistry Division, Department of Chemistry, Faculty of Science, Mansoura University, 35516 Mansoura, Egypt.; Department of Basic Sciences, Faculty of Applied Health Sciences, Horus University, Egypt.
Abstract:
Novel thiazole and thiophene derivatives were developed as aldose reductase (ALR2) inhibitors with intrinsic antioxidant activity to address diabetic complications associated with the polyol pathway. A series of compounds 3, 4a-c, 8, 9a-b, 10, 12 and 13a-c were evaluated for in vitro ALR2 inhibitory activity, particularly congeners 8 and 10 demonstrated potent inhibition with IC50 values of 1.965 ± 0.185 and 2.135 ± 0.168 μM, respectively, comparable to the reference epalrestat (IC50 = 2.726 ± 0.292 μM). Based on the more favorable docking results, derivative 8 was further evaluated in STZ-induced diabetic mice at 10 mg/kg (i.p.) for 15 days. Treatment attenuated oxidative stress, as evidenced by reduced malondialdehyde (MDA) levels and enhanced antioxidant enzyme activities, including SOD, CAT, and GPx compared with diabetic controls (p < 0.05). In addition, treatment significantly improved the serum lipid parameters by reducing total cholesterol (TC), triglycerides (TG), and LDL-C levels, while increasing HDL-C levels (p < 0.05). Furthermore, hepatic and renal biochemical markers, together with histopathological examination, demonstrated protective effects of compound 8 against diabetes-associated tissue damage. Molecular docking studies suggested favorable binding interactions of compound 8 to key ALR2 active site residues, particularly Trp111, while MD simulations further supported the stability of the ALR2-8 complex. Hence, the combined biological and computational results establish compound 8 as an auspicious ALR2 candidate inhibitor with potential in vivo antioxidant activity for further development.
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