Methyl 2-(2-chloroethylaminocarbonyl)diazenecarboxylate SB-166 inhibits the growth of different tumour cell lines, including drug-resistant sublines

Recently we synthesized new drugs, diazenecarboxamides (shortly diazenes), that were cytotoxic for several tumour cell lines. Because the solubility and biological activity of these drugs was relatively low, new compounds have been synthesized. In the present study we examined the cytotoxic effect of nine compounds: an imidazolidin-2-one (SB-282: methyl 5-benzoyl-3-(2-chloroethyl)-2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-ylcarbamate), two diazenecarboxamides (UP-140: N-phenyl-2-(2-quinolinyl)diazene-carboxamide; JK-1090: N-(4-iodophenyl)-2-(2-pyridinyl)diazenecarboxamide), two aminocarbonyl substituted diazenecarboxylates (SB-178: methyl 2-[(cyclohexylamino)carbonyl]diazenecarboxylate; SB-166: methyl 2-{[(2-chloroethyl)amino]carbonyl}diazenecarboxylate) and four diazenedicarboxamides (SB-410: N-1-(2-chloroethyl)-N-2-(2-pyridinylmethyl)-1,2-diazenedicarboxamide; SB-472: N-1-(2-chloroethyl)-N-2-(4-isopropylphenyl)-1,2-diazenedicarboxamide; SB-503: N-1-(4-sec-butylphenyl)-N2-(2-chloroethyl)-1,2-diazenedicarboxamide; SB-474: N-1-(4-tert-butylphenyl)-N-2-(2-chloroethyl)-1,2-diazenedicarboxamide). Using a modified colorimetric MTT assay, their cytotoxicity was determined on eight human cell lines: laryngeal carcinoma parental and two drug-resistant cell lines, glioblastoma parental and drug-resistant cell lines, cervical carcinoma parental and drug-resistant cell lines and breast adenocarcinoma cells. Results show that diazene SB-166 was very effective, reducing significantly the cell survival of all eight examined cell lines, including four drug-resistant cell lines. Compound SB-410 was cytotoxic for all examined cell lines, but mostly only in the highest concentration. Other compounds were not significantly cytotoxic to any of the treated cell lines. Our results, especially those obtained on drug-resistant cells, encourage further research on compound SB-166 as a potential anticancer drug. (C) 2003 Elsevier Science Ltd. All rights reserved.