RESUMEN

The synthesis of a series of novel 3,4-cis- and 3,4-trans-substituted carbocyclic nucleoside analogs from protected uracil and thymine is described. The key reaction in the followed synthetic protocols utilized the Mitsunobu reaction to couple 3,4-substituted cyclopentanols to (3)N-benzoyl uracil or (3)N-benzoyl thymine. These molecules were evaluated with regard to their ability to treat diabetic nephropathy. Our results show that two analogs significantly reduced high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro and, more interestingly, exhibited an anti-oxidative effect suggesting that the activity may be mediated through ROS-dependent mechanism.

Asunto(s)

Proteínas de la Matriz Extracelular/metabolismo , Nucleósidos/química , Especies Reactivas de Oxígeno/metabolismo , Actinas/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/patología , Fibronectinas/metabolismo , Mesangio Glomerular/citología , Mesangio Glomerular/metabolismo , Glucosa/farmacología , Nucleósidos/síntesis química , Nucleósidos/farmacología , Ratas