Author/Authors :
Jang-Yang Chang، نويسنده , , Chyun-Feng Lin، نويسنده , , Wen-Yu Pan، نويسنده , , Valeriy Bacherikov، نويسنده , , Ting-Chao Chou، نويسنده , , Ching-Huang Chen، نويسنده , , Huajin Dong، نويسنده , , Shu-Yun Cheng، نويسنده , , Tsong-Jen Tasi، نويسنده , , Yi-Wen Lin، نويسنده , , Kuo-Tung Chen، نويسنده , , Li-Tzong Chen، نويسنده , , Tsann-Long Su، نويسنده ,
Abstract :
A series of new analogues of 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA, 1) and AHMA-ethylcarbamate (2) were synthesized by introducing an O-alkylcarboxylic acid esters to the CH2OH function, displacing the CH2OH function with a dimethylaminocarboxamido group or with a methyl function introduced at the meta-, para- or ortho-position to the NH2 group to form 5-(9-acridinylamino)-m-toluidines (AMTs), 5-(9-acridinylamino)-p-toluidines (APTs) or 5-(9-acridinylamino)-o-toluidines (AOTs), respectively. The inhibitions of a variety of human tumor cell growth, interactions with DNA as well as inhibitory effect against topoisomerase II (Topo II) of these new agents were studied. Among AMT, APT and AOT derivatives with dimethylaminoethylcarboxamido and Me at C4 and C5 of acridine moiety (i.e., 21c, 23c and 26c) were more cytotoxic than AHMA (1) and AHMA-ethylcarbamate (2), depending upon the tumor cell line tested. Detailed structure–activity relationships of the new analogues were studied.
