Effect of side chain location in (2-aminoethyl)-aminomethyl-2-phenylquinolines as antitumor agents.

Three new derivatives of 2-phenylquinoline having an (2-aminoethyl)aminomethyl group in 7-, 6-, or 4'- (para position of 2-phenyl ring) positions of aromatic system have been prepared. The antitumor activity of these compounds together with 8- or 4- substituted isomers against the HeLa cell is in the order of 8- > 7- > 4- approximately 6- approximately 4'- substituted ones, which is almost in good agreement with that of DNA-binding ability evaluated by means of DNA-titration of UV-VIS spectra, DNA melting experiment, and ethidium displacement assay. Two representative compounds (8- and 4- isomers) are confirmed to have an ability to intercalate into double stranded DNA by topoisomerase I superhelix unwinding assay.