title: New analogues of AHMA as potential antitumor agents: synthesis and biological activity.
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 CH(2)OH function, displacing the CH(2)OH function with a dimethylaminocarboxamido group or with a methyl function introduced at the meta-, para- or ortho-position to the NH(2) 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.
authors: Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan.
authors: Jang-Yang
authors: JY
authors: Chang
authors: Chyun-Feng
authors: CF
authors: Lin
authors: Wen-Yu
authors: WY
authors: Pan
authors: Valeriy
authors: V
authors: Bacherikov
authors: Ting-Chao
authors: TC
authors: Chou
authors: Ching-Huang
authors: CH
authors: Chen
authors: Huajin
authors: H
authors: Dong
authors: Shu-Yun
authors: SY
authors: Cheng
authors: Tsong-Jen
authors: TJ
authors: Tasi
authors: Yi-Wen
authors: YW
authors: Lin
authors: Kuo-Tung
authors: KT
authors: Chen
authors: Li-Tzong
authors: LT
authors: Chen
authors: Tsann-Long
authors: TL
authors: Su
mesh_terms: D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D013329:Structure-Activity Relationship
chemical_list: C466640:3-(9-acridinylamino)-5-hydroxymethylaniline; D000166:Acridines; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors