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

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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
Issue number12
Publication statusPublished - Jun 15 2006
Externally publishedYes


ASJC Scopus subject areas

  • Organic Chemistry

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