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Synthesis and DNA‐Damaging Properties of Cisplatin‐ N ‐Mustard Conjugates
Author(s) -
Schiesser Stefan,
Hackner Benjamin,
Vrabel Milan,
Beck Wolfgang,
Carell Thomas
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201500144
Subject(s) - chemistry , cisplatin , dna , conjugate , dna damage , adduct , dna synthesis , stereochemistry , combinatorial chemistry , nitrogen mustard , dna repair , biochemistry , organic chemistry , medicine , surgery , mathematical analysis , mathematics , chemotherapy , cyclophosphamide
Abstract 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.