title: 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.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Naval
authors.initials: N
authors.lastname: Kapuriya
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kakadiya
authors.forename: Huajin
authors.initials: H
authors.lastname: Dong
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Pei-Chih
authors.initials: PC
authors.lastname: Lee
authors.forename: Xiuguo
authors.initials: X
authors.lastname: Zhang
authors.forename: Ting-Chao
authors.initials: TC
authors.lastname: Chou
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.forename: Ching-Huang
authors.initials: CH
authors.lastname: Chen
authors.forename: King
authors.initials: K
authors.lastname: Lam
authors.forename: Bhavin
authors.initials: B
authors.lastname: Marvania
authors.forename: Anamik
authors.initials: A
authors.lastname: Shah
authors.forename: Tsann-Long
authors.initials: TL
authors.lastname: Su
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D057230:Limit of Detection; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009150:Mustard Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014867:Water; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009150:Mustard Compounds; D014867:Water