Antitumor studies -- part 2: structure-activity relationship study for flavin analogs including investigations on their in vitro antitumor assay and docking simulation into protein tyrosine kinase.

Various analogs of flavins, 5-deazaflavins, and flavin-5-oxides were docked into the binding site of protein tyrosine kinase pp60(c-src), and some of them were assayed for their potential antitumor and PKC (protein kinase C) inhibitory activities in vitro. The results considering SAR (structure-activity relationship) revealed that the higher binding affinities obtained include compounds with the structure modifications on the flavin or 5-deazaflavin skeleton, namely, NH(2) or Ph (phenyl-) group at the C-2 position and so on. Computationally designed compounds 4a, 6a, b, 7, 11b, c, 12, 15, and 22c exhibited good docking results suggesting that they are potentially active antitumor agents. These compounds have 1-3 phenyl moieties, which are thought to be responsible for the planar aromatic fitting or electrostatic attraction onto the groove of the binding pocket.