New analogues of AHMA as potential antitumor agents: synthesis and biological activity.
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.
Chang
Jang-Yang
JY
Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan.
Lin
Chyun-Feng
CF
Pan
Wen-Yu
WY
Bacherikov
Valeriy
V
Chou
Ting-Chao
TC
Chen
Ching-Huang
CH
Dong
Huajin
H
Cheng
Shu-Yun
SY
Tasi
Tsong-Jen
TJ
Lin
Yi-Wen
YW
Chen
Kuo-Tung
KT
Chen
Li-Tzong
LT
Su
Tsann-Long
TL
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
C466640:3-(9-acridinylamino)-5-hydroxymethylaniline; D000166:Acridines; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors