Synthesis and biological activity of 2,5-diaryl-3-methylpyrimido[4,5-c]quinolin-1(2H)-one derivatives.

Abstract A series of 2,5-diaryl-3-methylpyrimido[4,5- c ]quinolin-1(2 H )-ones ( 7 – 30 ), variously substituted at the 2- and 5-phenyl moieties, were synthesized and evaluated for their in vitro cytotoxic activity against a PC3 cancer cell line. Cytotoxicity data revealed that the type of substituent as well as substitution pattern have variable influence on cytotoxic activity. Among the compounds tested, compounds ( 9 ), ( 13 ), ( 18 ), ( 19 ), and ( 23 ) demonstrated appreciable cytotoxic activity with mean IC 50 values of 2.0, 1.4, 1.6, 2.2, and 1.9 μM, respectively. Methyl substitution at the 2-phenyl ring was found to yield the least active compounds. Two of the most potent compounds ( 13 ) and ( 18 ) were further investigated for inhibition of tubulin polymerization and found to have no activity at the concentrations used in the assay.