Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu. II. Acylhydrazone-functionalized pyrimidines
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Elsevier Ltd
Abstract
We report herein the synthesis of a novel series of carbocyclic acylhydrazone derivatives of uracil, thymine and cytosine from the corresponding nucleic bases and their biological activity to treat diabetic nephropathy. Intriguingly, five derivatives significantly reduced high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro. The anti-oxidative effects displayed by these molecules suggest that their activity might involve a ROS-dependent mechanism.
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Actins/metabolism, Animals, Cell proliferation/drug effects, Cells, cultured, Diabetes mellitus, type 2/metabolism/pathology, Fibronectins/metabolism, Glucose/pharmacology, Mesangial cells/cytology/drug effects/metabolism, Nucleosides/chemical synthesis/chemistry/pharmacology, Pyrimidines/chemical synthesis/chemistry/pharmacology, Rats, Reactive oxygen species/metabolism, Acylhydrazones, Carbocyclic nucleosides, Cytosine, Diabetic nephropathy, Thymine, Uracil