TY - JOUR
T1 - Design, synthesis, and pharmacological evaluation of novel hybrid compounds to treat sickle cell disease symptoms
AU - Dos Santos, Jean Leandro
AU - Lanaro, Carolina
AU - Lima, Ldia Moreira
AU - Gambero, Sheley
AU - Franco-Penteado, Carla Fernanda
AU - Alexandre-Moreira, Magna Suzana
AU - Wade, Marlene
AU - Yerigenahally, Shobha
AU - Kutlar, Abdullah
AU - Meiler, Steffen E.
AU - Costa, Fernando Ferreira
AU - Chung, Manchin
PY - 2011/8/25
Y1 - 2011/8/25
N2 - A 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 α (TNFα). Unlike hydroxyurea, the compounds reduced the concentrations of TNFα to levels similar to those induced with the control dexamethasone (300 μMol/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.
AB - A 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 α (TNFα). Unlike hydroxyurea, the compounds reduced the concentrations of TNFα to levels similar to those induced with the control dexamethasone (300 μMol/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.
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U2 - 10.1021/jm200531f
DO - 10.1021/jm200531f
M3 - Article
C2 - 21766854
AN - SCOPUS:80051880495
SN - 0022-2623
VL - 54
SP - 5811
EP - 5819
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 16
ER -