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 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.
Di Francesco
A M
AM
Department of Biological Sciences, Salford University, UK.
Hargreaves
R H
RH
Wallace
T W
TW
Mayalarp
S P
SP
Hazrati
A
A
Hartley
J A
JA
Butler
J
J
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
D000970:Antineoplastic Agents; D016227:Benzoquinones; D003432:Cross-Linking Reagents; D004952:Esters; D007202:Indicators and Reagents; D016660:NAD(P)H Dehydrogenase (Quinone); D004950:Esterases