New analogues of AHMA as potential antitumor agents: Synthesis and biological activity

Jang Yang Chang; Chyun Feng Lin; Wen Yu Pan; Valeriy Bacherikov; Ting Chao Chou; Ching Huang Chen; Huajin Dong; Shu Yun Cheng; Tsong Jen Tasi; Yi Wen Lin; Kuo Tung Chen; Li Tzong Chen; Tsann Long Su

doi:10.1016/j.bmc.2003.09.001

New analogues of AHMA as potential antitumor agents: Synthesis and biological activity

Jang Yang Chang, Chyun Feng Lin, Wen Yu Pan, Valeriy Bacherikov, Ting Chao Chou, Ching Huang Chen, Huajin Dong, Shu Yun Cheng, Tsong Jen Tasi, Yi Wen Lin, Kuo Tung Chen, Li Tzong Chen, Tsann Long Su

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	4959-4969
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	11
Issue number	23
DOIs	https://doi.org/10.1016/j.bmc.2003.09.001
Publication status	Published - Nov 2003
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2003.09.001

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@article{79bc2b8621f64bc084e520ee5cb598d5,

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 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 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.",

author = "Chang, {Jang Yang} and Lin, {Chyun Feng} and Pan, {Wen Yu} and Valeriy Bacherikov and Chou, {Ting Chao} and Chen, {Ching Huang} and Huajin Dong and Cheng, {Shu Yun} and Tasi, {Tsong Jen} and Lin, {Yi Wen} and Chen, {Kuo Tung} and Chen, {Li Tzong} and Su, {Tsann Long}",

note = "Funding Information: This work was supported by the National Science Council of Taiwan (Grant No. NSC90-2320-B-001-032). ",

year = "2003",

month = nov,

doi = "10.1016/j.bmc.2003.09.001",

language = "English",

volume = "11",

pages = "4959--4969",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

number = "23",

}

TY - JOUR

T1 - New analogues of AHMA as potential antitumor agents

T2 - Synthesis and biological activity

AU - Chang, Jang Yang

AU - Lin, Chyun Feng

AU - Pan, Wen Yu

AU - Bacherikov, Valeriy

AU - Chou, Ting Chao

AU - Chen, Ching Huang

AU - Dong, Huajin

AU - Cheng, Shu Yun

AU - Tasi, Tsong Jen

AU - Lin, Yi Wen

AU - Chen, Kuo Tung

AU - Chen, Li Tzong

AU - Su, Tsann Long

N1 - Funding Information: This work was supported by the National Science Council of Taiwan (Grant No. NSC90-2320-B-001-032).

PY - 2003/11

Y1 - 2003/11

N2 - 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 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.

AB - 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 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.

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EP - 4969

JO - Bioorganic and Medicinal Chemistry

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IS - 23

ER -

New analogues of AHMA as potential antitumor agents: Synthesis and biological activity

Abstract

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