Synthesis and cytotoxic evaluation of certain 4-(phenylamino)furo[2,3-b]quinoline and 2-(furan-2-yl)-4-(phenylamino)quinoline derivatives.
Certain 4-(phenylamino)furo[2,3-b]quinoline and 2-(furan-2-yl)-4-(phenylamino)quinoline derivatives were synthesized and evaluated in vitro against the full panel of NCIs 60 cancer cell lines. The preliminary results indicated these tricyclic 4-(phenylamino)furo[2,3-b]quinolines were more cytotoxic than their corresponding 2-(furan-2-yl)-4-(phenylamino)quinoline isomers. For the 4-(phenylamino)furo[2,3-b]quinolines, compounds 2a and 3d are two of the most potent with a mean GI50 value of 0.025 microM in each case. Inactivity of 2b and 2c (positional isomers of 2a) indicated that both electronic environment, and the distance between intercalating pharmacophore and H-bond-donating MeO group are important. For the 2-(furan-2-yl)-4-(phenylamino)quinoline isomers, compound 12 (a mean GI50 of 4.36 microM), which bears a para-COMe substituent, is more active than its meta-substituted counterpart 13 (10.5 microM). However, the electron-donating MeO substituent is preferred at the meta-position, and the cytotoxicity for the meta-substituted derivatives decreased in the order: MeO derivative 14b (3.05 microM) > oxime 16 (6.85 microM) > ketone 13 (10.5 microM) > methyl oxime 18 (20.6 microM).
Zhao
Yue-Ling
YL
Faculty of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
Chen
Yeh-Long
YL
Tzeng
Cherng-Chyi
CC
Chen
I-Li
IL
Wang
Tai-Chi
TC
Han
Chien-Hwa
CH
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D005663:Furans; D011804:Quinolines