Design, synthesis, and biological evaluation of novel water-soluble N-mustards as potential anticancer agents.

Abstract	A series of novel water-soluble N-mustard-benzene conjugates bearing a urea linker were synthesized. The benzene moiety contains various hydrophilic side chains are linked to the meta- or para-position of the urea linker via a carboxamide or an ether linkage. The preliminary antitumor studies revealed that these agents exhibited potent cytotoxicity in vitro and therapeutic efficacy against human tumor xenografts in vivo. Remarkably, complete tumor remission in nude mice bearing human breast carcinoma MX-1 xenograft and significant suppression against prostate adenocarcinoma PC3 xenograft were achieved by treating with compound 9aa' at the maximum tolerable dose with relatively low toxicity. We also demonstrate that the newly synthesized compounds are able to induce DNA cross-linking through alkaline agarose gel shift assay. A pharmacokinetic profile of the representative 9aa' in rats was also investigated. The current studies suggest that this agent is a promising candidate for preclinical studies.
Authors	Naval Kapuriya, Rajesh Kakadiya, Huajin Dong, Amit Kumar, Pei-Chih Lee, Xiuguo Zhang, Ting-Chao Chou, Te-Chang Lee, Ching-Huang Chen, King Lam, Bhavin Marvania, Anamik Shah, Tsann-Long Su
Journal	Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 19 Issue 1 Pg. 471-85 (Jan 01 2011) ISSN: 1464-3391 [Electronic] England
PMID	21106377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright Â© 2010 Elsevier Ltd. All rights reserved.
Chemical References	Antineoplastic Agents Mustard Compounds Water
Topics	Animals Antineoplastic Agents (chemical synthesis, chemistry, pharmacology) Cell Cycle (drug effects) Cell Line, Tumor Dose-Response Relationship, Drug Drug Design Drug Screening Assays, Antitumor Humans Limit of Detection Male Mice Mice, Nude Mustard Compounds (chemical synthesis, chemistry, pharmacology) Rats Rats, Sprague-Dawley Solubility Water Xenograft Model Antitumor Assays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!