Potent antitumor 9-anilinoacridines and acridines bearing an alkylating N-mustard residue on the acridine chromophore: synthesis and biological activity.

Abstract	A series of 9-anilinoacridine and acridine derivatives bearing an alkylating N-mustard residue at C4 of the acridine chromophore were synthesized. The N-mustard pharmacophore was linked to the C4 of the acridine ring with an O-ethyl (O-C(2)), O-propyl (O-C(3)), or O-butyl (O-C(4)) 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.
Authors	Tsann-Long Su, Yi-Wen Lin, Ting-Chao Chou, Xiuguo Zhang, Valeriy A Bacherikov, Ching-Huang Chen, Leroy F Liu, Tsong-Jen Tsai
Journal	Journal of medicinal chemistry (J Med Chem) Vol. 49 Issue 12 Pg. 3710-8 (Jun 15 2006) ISSN: 0022-2623 [Print] United States
PMID	16759114 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Acridines Aminoacridines Aniline Compounds Antineoplastic Agents, Alkylating N1-(4-(2-(bis(2-chloroethyl)amino)ethoxy)acridin-9-yl)-5-methoxybenzene-1,3-diamine N1-(4-(4-(bis(2-chloroethyl)amino)butoxy)acridin-9-yl)-5-methoxybenzene-1,3-diamine Nitrogen Mustard Compounds DNA DNA Topoisomerases, Type II
Topics	Acridines (chemical synthesis, chemistry, pharmacology) Aminoacridines (chemical synthesis, chemistry, pharmacology) Aniline Compounds (chemical synthesis, chemistry, pharmacology) Animals Antineoplastic Agents, Alkylating (chemical synthesis, chemistry, pharmacology) Cell Line, Tumor DNA (chemistry) DNA Topoisomerases, Type II (chemistry) Drug Screening Assays, Antitumor Humans Male Mice Mice, Nude Neoplasm Transplantation Nitrogen Mustard Compounds (chemical synthesis, chemistry, pharmacology) Structure-Activity Relationship Transplantation, Heterologous

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