Potent antitumor 9-anilinoacridines and acridines bearing an alkylating N-mustard residue on the acridine chromophore: Synthesis and biological activity Journal Article
| Authors: | Su, T. L.; Lin, Y. W.; Chou, T. C.; Zhang, X.; Bacherikov, V. A.; Chen, C. H.; Liu, L. F.; Tsai, T. J. |
| Article Title: | 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 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. © 2006 American Chemical Society. |
| Keywords: | controlled study; leukemia; unclassified drug; human cell; dose response; drug efficacy; nonhuman; solid tumor; paclitaxel; antineoplastic agent; mouse; animals; mice; animal experiment; animal model; antineoplastic activity; drug potency; in vitro study; tumor xenograft; drug screening assays, antitumor; cell line, tumor; drug synthesis; structure-activity relationship; vinblastine; cancer inhibition; dna; nude mouse; mice, nude; breast carcinoma; antineoplastic agents, alkylating; transplantation, heterologous; alkylation; drug cytotoxicity; aniline compounds; neoplasm transplantation; ic 50; acridine derivative; acridines; dna topoisomerases, type ii; nitrogen mustard compounds; benzene derivative; cross resistance; gyrase inhibitor; cross linking reagent; aniline derivative; mustard gas derivative; n1 [4 [2 [bis(2 chloroethyl)amino]ethoxy]acridin 9 yl] 5 methoxybenzene 1,3 diamine; n1 [4 [2 [bis(2 chloroethyl)amino]ethoxy]acridin 9 yl] 5 methylbenzene 1,3 diamine; n1 [4 [4 [bis(2 chloroethyl)amino]butoxy]acridin 9 yl] 5 methoxybenzene 1,3 diamine; n1 [4 [4 [bis(2 chloroethyl)amino]butoxy]acridin 9 yl] 5 methylbenzene 1,3 diamine; n3 [4 [4 [bis(2 chloroethyl)amino]butoxy]acridin 9 yl] 4 methylbenzene 1,3 diamine; aminoacridines |
| Journal Title: | Journal of Medicinal Chemistry |
| Volume: | 49 |
| Issue: | 12 |
| ISSN: | 0022-2623 |
| Publisher: | American Chemical Society |
| Date Published: | 2006-06-15 |
| Start Page: | 3710 |
| End Page: | 3718 |
| Language: | English |
| DOI: | 10.1021/jm060197r |
| PUBMED: | 16759114 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 18" - "Export Date: 4 June 2012" - "CODEN: JMCMA" - "Source: Scopus" |
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