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 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.
UMR 484 INSERM-Université d'Auvergne-Centre Jean Perrin, Rue Montalembert BP 184, 63005 Clermont-Ferrand, France.
Elisabeth
E
Miot-Noirault
Jean
J
Legault
Florent
F
Cachin
Emmanuelle
E
Mounetou
Françoise
F
Degoul
René C
RC
Gaudreault
Nicole
N
Moins
Jean Claude
JC
Madelmont
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D000970:Antineoplastic Agents; C503407:N-(4-tert-butylphenyl)-N'-(2-chloroethyl)urea; D010671:Phenylurea Compounds