Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage Journal Article
| Authors: | Kapuriya, N.; Kapuriya, K.; Zhang, X.; Chou, T. C.; Kakadiya, R.; Wu, Y. T.; Tsai, T. H.; Chen, Y. T.; Lee, T. C.; Shah, A.; Naliapara, Y.; Su, T. L. |
| Article Title: | Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage |
| Abstract: | To improve the chemical stability and therapeutic efficacy of N-mustard, a series of phenyl N-mustard linked to DNA-affinic 9-anilinoacridines and acridine via a urea linker were synthesized and evaluated for antitumor studies. The new N-mustard derivatives were prepared by the reaction of 4-bis(2-chloroethyl)aminophenyl isocyanate with a variety of 9-anilinoacridines or 9-aminoacridine. The antitumor studies revealed that these agents exhibited potent cytotoxicity in vitro without cross-resistance to taxol or vinblastine and showed potent antitumor therapeutic efficacy in nude mice against human tumor xenografts. It also showed that 24d was capable of inducing marked dose-dependent levels of DNA cross-linking by comet assay and has long half-life in rat plasma. © 2008 Elsevier Ltd. All rights reserved. |
| Keywords: | controlled study; human cell; nonhuman; antineoplastic agents; antineoplastic agent; cell proliferation; mouse; animals; mice; animal experiment; animal model; antineoplastic activity; cytotoxicity; drug potency; drug structure; in vitro study; dose-response relationship, drug; drug screening assays, antitumor; xenograft model antitumor assays; cell line, tumor; drug synthesis; mus musculus; dna; biological activity; xenograft; mice, nude; glioma cell; molecular structure; rats; rattus; 9-anilinoacridines; cytotoxic; 9 anilinoacridine derivative; amsacrine; drug half life; inhibitory concentration 50; reaction analysis; drug stability; concentration response; dna cross linking; acridines; brassicaceae; chlormethine derivative; stereoisomerism; cross resistance; urea; comet assay; aniline nitrogen mustards; dna alkylating agents; 1 [4 [bis(2 chloroethyl)amino]phenyl] 3 [2 methyl 5 (4 methylacridin 9 ylamino)phenyl]urea; 4 bis(2 chloroethyl)aminophenylisocyanate; aniline derivative; isocyanic acid derivative; aniline mustard |
| Journal Title: | Bioorganic & Medicinal Chemistry |
| Volume: | 16 |
| Issue: | 10 |
| ISSN: | 0968-0896 |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 2008-01-01 |
| Start Page: | 5413 |
| End Page: | 5423 |
| Language: | English |
| DOI: | 10.1016/j.bmc.2008.04.024 |
| PUBMED: | 18450456 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "CODEN: BMECE" - "Source: Scopus" |
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