The abnormal cytotoxicities of 2,5-diaziridinyl-1,4-benzoquinone-3-phenyl esters

Several derivatives of 2,5-diaziridinyl-3-phenyl-1,4-benzoquinone have been synthesized and their cytotoxicities in six different human cancer cell li nes (H460, H596, HT29, BE, K562 and A2780) have been determined. It was obs erved that certain phenol-ester derivatives were significantly more cytotox ic in all of the cell lines investigated, These esters were shown to be cle aved by esterases to form a stable meta-phenol and an unstable para-phenol, The meta-phenol was also highly cytotoxic, Several of these compounds were studied in detail using DNA cross-linking, clonogenic, apoptosis and flow cytometry assays. It is proposed that although the phenol-esters and the ph enols can efficiently cross-link DNA, this mechanism alone is not sufficien t to explain the toxicities of these compounds.