Potent antitumor 9-anilinoacridines and acridines bearing an alkylating N-mustard residue on the acridine chromophore

Synthesis and biological activity

Tsann Long Su, Yi W. Lin, Ting Chao Chou, Xiuguo Zhang, Valeriy A. Bacherikov, Ching Huang Chen, Leroy-Fong Liu, Tsong J. Tsai

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

A series of 9-anilinoacridine and acridine derivatives bearing an alkylating N-mustard residue at C 4 of the acridine chromophore were synthesized. The N-mustard pharmacophore was linked to the C 4 of the acridine ring with an O-ethyl (O-C2), O-propyl (O-C3), or O-butyl (O-C4) spacer. It revealed that all newly synthesized compounds were very potent cytotoxic agents against human leukemia and various solid tumors in vitro. These agents did not exhibit cross-resistance against vinblastine-resistant (CCRF-CEM/VBL) or taxol-resistant (CCRF-CEM/taxol) cells. It also showed that these agents were DNA cross-linking agents rather than topoisomerase II inhibitors. Of these agents, compounds 27a and 27c were shown to have potent antitumor activity in nude mice bearing the human breast carcinoma MX-1 xenograft. The therapeutic efficacies of these two agents are comparable to that of taxol.

Original languageEnglish
Pages (from-to)3710-3718
Number of pages9
JournalJournal of Medicinal Chemistry
Volume49
Issue number12
DOIs
Publication statusPublished - Jun 15 2006
Externally publishedYes

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Bearings (structural)
Acridines
Mustard Plant
Chromophores
Bioactivity
Paclitaxel
Topoisomerase II Inhibitors
Vinblastine
Cytotoxins
Heterografts
Nude Mice
Leukemia
Breast Neoplasms
DNA
Tumors
9-anilinoacridine
Neoplasms
Derivatives
Therapeutics

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Potent antitumor 9-anilinoacridines and acridines bearing an alkylating N-mustard residue on the acridine chromophore : Synthesis and biological activity. / Su, Tsann Long; Lin, Yi W.; Chou, Ting Chao; Zhang, Xiuguo; Bacherikov, Valeriy A.; Chen, Ching Huang; Liu, Leroy-Fong; Tsai, Tsong J.

In: Journal of Medicinal Chemistry, Vol. 49, No. 12, 15.06.2006, p. 3710-3718.

Research output: Contribution to journalArticle

Su, Tsann Long ; Lin, Yi W. ; Chou, Ting Chao ; Zhang, Xiuguo ; Bacherikov, Valeriy A. ; Chen, Ching Huang ; Liu, Leroy-Fong ; Tsai, Tsong J. / Potent antitumor 9-anilinoacridines and acridines bearing an alkylating N-mustard residue on the acridine chromophore : Synthesis and biological activity. In: Journal of Medicinal Chemistry. 2006 ; Vol. 49, No. 12. pp. 3710-3718.
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AU - Lin, Yi W.

AU - Chou, Ting Chao

AU - Zhang, Xiuguo

AU - Bacherikov, Valeriy A.

AU - Chen, Ching Huang

AU - Liu, Leroy-Fong

AU - Tsai, Tsong J.

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