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 int...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2003-11, Vol.11 (23), p.4959-4969
Main Authors: CHANGE, Jang-Yang, LIN, Chyun-Feng, CHEN, Kuo-Tung, CHEN, Li-Tzong, SU, Tsann-Long, PAN, Wen-Yu, BACHERIKOV, Valeriy, CHOU, Ting-Chao, CHEN, Ching-Huang, HUAJIN DONG, CHENG, Shu-Yun, TASI, Tsong-Jen, LIN, Yi-Wen
Format: Article
Language:English
Subjects:
Acridines - chemical synthesis
Acridines - chemistry
Acridines - pharmacology
Aniline Compounds - chemical synthesis
Aniline Compounds - chemistry
Aniline Compounds - pharmacology
Animals
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cell Division - drug effects
Cell Line, Tumor
Enzyme Inhibitors - pharmacology
General aspects
Humans
Medical sciences
Mice
Pharmacology. Drug treatments
Structure-Activity Relationship
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Summary: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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2003.09.001