Design, synthesis, and pharmacological evaluation of novel hybrid compounds to treat sickle cell disease symptoms

Jean Leandro Dos Santos, Carolina Lanaro, Ldia Moreira Lima, Sheley Gambero, Carla Fernanda Franco-Penteado, Magna Suzana Alexandre-Moreira, Marlene Wade, Shobha Yerigenahally, Abdullah Kutlar, Steffen E. Meiler, Fernando Ferreira Costa, Manchin Chung

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28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5811-5819
Number of pages9
JournalJournal of Medicinal Chemistry
Volume54
Issue number16
DOIs
Publication statusPublished - Aug 25 2011

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Dos Santos, J. L., Lanaro, C., Lima, L. M., Gambero, S., Franco-Penteado, C. F., Alexandre-Moreira, M. S., ... Chung, M. (2011). Design, synthesis, and pharmacological evaluation of novel hybrid compounds to treat sickle cell disease symptoms. Journal of Medicinal Chemistry, 54(16), 5811-5819. https://doi.org/10.1021/jm200531f