Abstract
The synthesis of some new 3-cyano-1,4,6-trisubstituted-2(1
H
)-pyridinones supported with various pharmacophores and functionalities at positin-1 is described. The in vitro anticancer activity of 24 of the newly synthesized compounds was evaluated according to the protocol of the NCI in vitro disease-oriented human cells screening panel assay. The results revealed that five compounds
4a
–
c
,
7b
, and
12b
were able to display moderate antitumor potential against some of the tested subpanel tumor cell lines at the GI
50
and TGI levels, however, with marginal or no cytotoxic (LC
50
) activity. The obtained data suggested that better antitumor activity was linked to derivatives with either 4-bromophenyl or 3,4-dimethoxyphenyl moieties, together with a 1-methyl-1
H
-pyrrol-2-yl counter part at positions 6 and 4, respectively. Consequently, the 3-cyano-4-(1-methyl-1
H
-pyrrol-2-yl)-6-(4-bromophenyl or 3,4-dimethoxyphenyl)-2(1
H
)-pyridinones
4a
and
4b
, could be considered as the most active members identified in this investigation as evidenced from their relative higher growth inhibitory (GI
50
(MG-MID) 77.6 and 67.6 μM, respectively) and cytostatic (TGI (MG-MID) 85.1 and 95.5 μM, respectively) activities, when compared with the substituted thiocarbamoyl analog
7b
and the bicyclic [1,2,4]triazolo[3,4-a]pyridine derivative
12b
.