title: The abnormal cytotoxicities of 2,5-diaziridinyl-1,4-benzoquinone-3-phenyl esters.
abstract: Several derivatives of 2,5-diaziridinyl-3-phenyl-1,4-benzoquinone have been synthesized and their cytotoxicities in six different human cancer cell lines (H460, H596, HT29, BE, K562 and A2780) have been determined. It was observed that certain phenol-ester derivatives were significantly more cytotoxic in all of the cell lines investigated. These esters were shown to be cleaved 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 phenols can efficiently cross-link DNA, this mechanism alone is not sufficient to explain the toxicities of these compounds.
authors.affiliation: Department of Biological Sciences, Salford University, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Di Francesco
authors.forename: R H
authors.initials: RH
authors.lastname: Hargreaves
authors.forename: T W
authors.initials: TW
authors.lastname: Wallace
authors.forename: S P
authors.initials: SP
authors.lastname: Mayalarp
authors.forename: A
authors.initials: A
authors.lastname: Hazrati
authors.forename: J A
authors.initials: JA
authors.lastname: Hartley
authors.forename: J
authors.initials: J
authors.lastname: Butler
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002999:Clone Cells / Q000187:drug effects; D003432:Cross-Linking Reagents; D004586:Electrophoresis; D004950:Esterases / Q000737:chemistry; D004952:Esters / Q000138:chemical synthesis* / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007202:Indicators and Reagents; D008968:Molecular Conformation; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D003432:Cross-Linking Reagents; D004952:Esters; D007202:Indicators and Reagents; D016660:NAD(P)H Dehydrogenase (Quinone); D004950:Esterases