Antineoplastic potency of arylchloroethylurea derivatives in murine colon carcinoma

In a search for new antineoplastic agents the lead compound N-(4-tert-butylphenyl)-N'-(2-chloroethyl)urea (CEU-22) of a series of 1-aryl-3-(2-chloroethyl)ureas and its iodinated bioisostere CEU-98, were previously selected on the basis of their cytotoxicity and the potent tropism for the intest...

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Bibliographic Details
Published in:Investigational new drugs 2004-11, Vol.22 (4), p.369-378
Main Authors: Miot-Noirault, Elisabeth, Legault, Jean, Cachin, Florent, Mounetou, Emmanuelle, Degoul, Françoise, Gaudreault, René C, Moins, Nicole, Madelmont, Jean Claude
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacology
Cancer therapies
Cell Line, Tumor
Chemotherapy
Colorectal cancer
Colorectal Neoplasms - drug therapy
Cytotoxicity
Drug Administration Schedule
Drug dosages
Drug Screening Assays, Antitumor
Drugs
Experiments
Humans
Injections, Intraperitoneal
Laboratory animals
Leukemia
Male
Maximum Tolerated Dose
Medical prognosis
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
Phenylurea Compounds - administration & dosage
Phenylurea Compounds - pharmacology
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Summary:In a search for new antineoplastic agents the lead compound N-(4-tert-butylphenyl)-N'-(2-chloroethyl)urea (CEU-22) of a series of 1-aryl-3-(2-chloroethyl)ureas and its iodinated bioisostere CEU-98, were previously selected on the basis of their cytotoxicity and the potent tropism for the intestinal tract (evidenced for CEU-22). In this study, we investigated the antitumour profile of these two drugs for the indication of colon cancer. In vitro, we found that micromolar concentrations of both CEU-22 and CEU-98 inhibited proliferation of DLD-1, Caco-2, HT-29, SW-948 and CT-26 lines. In vivo, a high inhibition of tumour growth and a life span increase were observed when BALB/c mice grafted subcutaneously with CT-26 cells received 5 daily intratumoural injections of each drug. When administered by the intraperitoneal route according to an intermittent schedule starting Day 1 or Day 7 post-implant, only CEU-98 demonstrated antitumour activity ( T / C = 29% for the Day-1,5,9-treatment versus 40% for the Day-7,11,15-treatment) and a life span increase around 40% for the two protocols. These results make CEU-98 a candidate for further investigations with a view to developing an efficacious treatment of colorectal cancer.
ISSN:0167-6997
1573-0646
DOI:10.1023/B:DRUG.0000036679.12112.4c