Synthesis and anticancer evaluation of certain 4-anilinofuro[2,3-b]quinoline and 4-anilinofuro[3,2-c]quinoline derivatives

Certain linear 4-anilinofuro[2,3-b]quinoline and angular 4-anilinofuro[3,2-c]quinoline derivatives were synthesized and evaluated in vitro against the full panel of NCI's 60 cancer cell lines. For the linear 4-anilinofurc)[2,3-b]quinoline derivatives, 1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone (5a) is the most cytotoxic with a mean GI(50) value of 0.025 mu M. Substitution at either furo[2,3-b]quinoline ring (2a, 2b, and 5b) or 4-anilino moiety (3-7) led to a decrease of cytotoxicity. For the angular 4-anilinofuro[3,2-c]quinoline derivatives, (E)-1-[3(furo[3,2-c]quinolin-4-ylamino)phenyl]ethanone oxime (14a) exhibited potent inhibitory activities on UO-31, UACC-257, and UACC-62, with GI(50) values of 0.03, < 0.01, and < 0.01 mu M respectively. The same cytotoxicity profile was observed for its methyl counterpart, 14b, in which the GI(50) values against UO-31, UACC-257, and UACC-62 was < 0.01, 0.04 and < 0.01 mu M respectively. These results deserve full attention especially because 14a and 14b are relatively non-cytotoxic with the mean GI(50) value of 7.73 and 8.91 mu M respectively. (c) 2005 Elsevier SAS. All rights reserved.