Synthesis, biological activity screening and molecular modeling study of acylaminoacetamide derivatives
Makaleler > Tam Makale · 2015
Yazarlar: Güneş ÇOBAN, FADİME AYDIN KÖSE, Petek BALLAR KIRMIZIBAYRAK, Mehmet Varol PABUÇÇUOĞLU
MEDICINAL CHEMISTRY RESEARCH, SCI Expanded İndekslerine Giren Dergi, Uluslararası, 2015, cilt 24, ss 3710-3729
DOI: 10.1007/s00044-015-1419-4
Özet
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.