dos Santos, Jean Leandro [UNESP]Lanaro, CarolinaLima, Lidia MoreiraGambero, Sheley [UNESP]Franco-Penteado, Carla FernandaAexandre-Moreira, Magna SuzanaWade, MarleneYerigenahally, ShobhaKutlar, AbdullahMeiler, Steffen E.Costa, Fernando FerreiraChung, ManChin [UNESP]2014-05-202014-05-202011-08-25Journal of Medicinal Chemistry. Washington: Amer Chemical Soc, v. 54, n. 16, p. 5811-5819, 2011.0022-2623http://hdl.handle.net/11449/7800A novel series of thalidomide derivatives (4a-f) designed by molecular hybridization were synthesized and evaluated in vitro and in vivo for their potential use in the oral treatment of sickle cell disease symptoms. Compounds 4a-f demonstrated analgesic, anti-inflammatory, and NO-donor properties. Compounds 4c and 4d were considered promising candidate drugs and were further evaluated in transgenic sickle cell mice to determine their capacity to reduce the levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF alpha). Unlike hydroxyurea, the compounds reduced the concentrations of TNF alpha to levels similar to those induced with the control dexamethasone (300 mu mol/kg). These compounds are novel lead drug candidates with multiple beneficial actions in the treatment of sickle cell disease symptoms and offer an alternative to hydroxyurea treatment.5811-5819engArtigo10.1021/jm200531fWOS:000294077300014Acesso restrito97343336079754130000-0003-4141-0455