Design and synthesis of new anti-inflammatory steroids of Lapdesf FT-GL and GL-TAU series with potential anti-VEGF activity

Abstract

Glucocorticoids (GCs), steroidal anti-inflammatory drugs, are widely used in therapy mainly for their anti-inflammatory, immunosuppressive and antiangiogenic activities. They have the ability to reduce the transcription of several enzymes / inflammatory proteins such as cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS); proinflammatory cytokines and vascular endothelial growth factor (VEGF). The modulation of the cytokine tumor necrosis factor alpha (TNF-±), over expressed in many inflammatory diseases has become an interesting approach in the treatment of chronic inflammatory diseases, especially those patients who do not respond to conventional treatment. Thus, in the present study, have been planned by molecular hybridization strategy, new steroidal anti-inflammatory derivatives as modulators of TNF-± cytokine with potential anti-VEGF activity, useful in the treatment of chronic inflammatory diseases, including ocular diseases. In this context, will be synthesized and characterized prednisolone and budesonide derivatives of Lapdesf GL-FT and Lapdesf GL-TAU series. The compounds will be evaluated for anti-inflammatory activity in distal ulcerative colitis, production of proinflammatory cytokines, experimental determination of log P and VEGF expression. It is expected that the proposed derivatives exhibit anti-inflammatory and anti-VEGF activity superior to the standard (prednisolone and budesonide). (AU)