Synthesis, pharmacological evaluation and docking studies of new sulindac analogues

Nelilma C Romeiro; Ramon D F Leite; Lidia M Lima; Suzana V S Cardozo; Ana L P de Miranda; Carlos A M Fraga; Eliezer J Barreiro

doi:10.1016/j.ejmech.2008.11.012

Synthesis, pharmacological evaluation and docking studies of new sulindac analogues

Eur J Med Chem. 2009 May;44(5):1959-71. doi: 10.1016/j.ejmech.2008.11.012. Epub 2008 Dec 6.

Authors

Nelilma C Romeiro¹, Ramon D F Leite, Lidia M Lima, Suzana V S Cardozo, Ana L P de Miranda, Carlos A M Fraga, Eliezer J Barreiro

Affiliation

¹ Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, PO Box 68023, RJ 21944-970, Brazil.

PMID: 19144452
DOI: 10.1016/j.ejmech.2008.11.012

Abstract

This paper describes the synthesis, pharmacological evaluation and docking studies of a series of new sulindac analogues. Overall, the designed compounds revealed good, in vivo, antinociceptive activity and satisfactory anti-inflammatory profile. Flexible molecular docking with COX-1/COX-2 has shown putative binding modes of the designed compounds while the theoretical evaluation of cell permeability based on Lipinski's rule of five has helped rationalize the biological results.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry*
Cell Membrane Permeability
Computer Simulation
Cyclooxygenase 1 / metabolism
Cyclooxygenase 2 / metabolism
Drug Design*
Humans
Prodrugs
Protein Binding
Structure-Activity Relationship
Sulindac / analogs & derivatives*
Sulindac / pharmacology

Substances

Anti-Inflammatory Agents, Non-Steroidal
Prodrugs
Sulindac
Cyclooxygenase 1
Cyclooxygenase 2