Synthesis and cytotoxic evaluation of certain 4-anilino-2-phenylquinoline derivatives

The present report describes the synthesis and cell growth inhibition of certain 4-anilino-2-phenylquinoline derivatives. 4-(4-Acetylphenylamino)-6-methoxy-2-phenylquinoline (11), its oxime 15a, and its methyloxitne 15b. exhibited significant cylotoxicity against all 60 cancer cells with mean GI(50) values of 3.89, 3,02, and 3.89 pK respectively. while 4-(4-.icetylanilino)-6-methoxy-2-phenylquinoline-3-carboxylic acid (9) and its 3-carboxylic acid congeners 13a, 13b, 14a, and 14b were inactive, indicated free carboxylicacidat CO) position is unfavorable. The steric hindrance exerted by the 3-carboxylate in 9, 13, and 14 may prevent the adJacent phenyl ring to lie coplanar with quinoline, which leads to the devoid of cytotoxicity. The comparable cytotoxicity of oxime 15a, methyloxime 15b, and the ketone precursor 11 implied a hydrogen-bonding accepting group at C(4) position of 4-anilino-moiety is crucial for cytotoxicity, Among these compounds, It is especially active against the growth of certain solid cancer cells such as NCI-H226 (tion-sniall cell lung cancer), MDA-MB-231/ATCC (breast cancer), and SF-295 (CNS cancer) with GI(50) values of 0.94, 0.04, and < 0.01 mu M respectively, (c) 2005 Elsevier SAS. All rights reserved.