Details

Autor(en) / Beteiligte

• Schiesser, Stefan
• Hackner, Benjamin
• Vrabel, Milan
• Beck, Wolfgang
• Carell, Thomas

Titel

Synthesis and DNA-Damaging Properties of Cisplatin-N-Mustard Conjugates

Ist Teil von

• European journal of organic chemistry, 2015-04, Vol.2015 (12), p.2654-2660

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• We report the synthesis of two novel cisplatin‐N‐mustard conjugates. In these compounds two potentially DNA‐damaging molecules are combined and are separated by a spacer containing either one or four ethylene glycol units. We have shown that these conjugates are capable of forming novel clustered DNA adducts, thereby strongly increasing the lesion density in double‐stranded DNA, which is thought to block DNA repair and translesion synthesis. Their ability to inhibit cell division was proven in an E. coli assay. Two cisplatin‐N‐mustard conjugates have been synthesized with the two cytotoxic groups separated by one or four ethylene glycol units. MS analyses of their reactions with DNA duplexes proved that both cytotoxic groups can bind to DNA, leading to a variety of DNA lesions that should hamper the repair machinery of tumor cells to counteract cisplatin resistance. Both conjugates inhibit cell division.