Synthesis, biological activity screening and molecular modeling study of acylaminoacetamide derivatives

ÇOBAN G. , Kose F. , Kirmizibayrak P. , Pabuccuoglu V.

MEDICINAL CHEMISTRY RESEARCH, vol.24, no.10, pp.3710-3729, 2015 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 24 Issue: 10
  • Publication Date: 2015
  • Doi Number: 10.1007/s00044-015-1419-4
  • Page Numbers: pp.3710-3729


In this study, non-rigid analogs of thalidomide have been designed in order to develop potentially active, more effective and safer lead molecules for disorders caused or contributed by inflammation. Five different series of acylaminoacetamide compounds were synthesized, and the biological inhibitory potency of the title compounds has been determined by evaluating their effects on COX-2 isoenzyme expression and PGE(2) production in A549 (human lung adenocarcinoma) cell lines. Among the studied series, N-[2-(isopropylamino)-2-oxoethyl]isonicotinamide is the most active inhibitory compound on COX-2 isoenzyme expression, and N-[2-oxo-2-(pyrolydine-1-yl)etyl]isonicotinamide is the most active inhibitory compound on the biosynthesis of PGE(2). Molecular docking studies and molecular dynamics simulations were also applied to investigate non-covalent interactions of the most active compounds inside the active side of the crystal structure of murine cyclooxygenase 2 (mCOX-2) isoenzyme.