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.
Mikata
Y
Y
Department of Chemistry, Faculty of Science, Nara Women's University, Japan.
Yokoyama
M
M
Ogura
S
S
Okura
I
I
Kawasaki
M
M
Maeda
M
M
Yano
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004278:DNA, Superhelical / Q000187:drug effects; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D007202:Indicators and Reagents; D011804:Quinolines; D004247:DNA