Compounds that bind in the minor groove of DNA have found use in the experimental treatment of cancer and certain infectious diseases. Furthermore, agents which target and can recognize discrete sequences of DNA have the potential to offer selective therapies by modulating the activity of specific transcription factors or genes. For this reason, a number of sequence-selective DNA binding agents have been evaluated with a range of affinities and recognition fidelities. In this respect, the pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are of interest as they bind to guanine residues in the minor groove with a preference for Pu-G-Pu sequences. A dramatic increase in cytotoxicity and sequence selectivity has been achieved by linking two PBD units to form PBD dimers as cross-linking agents on opposite DNA strands (e.g., interstrand cross-links). SJG-136 is currently undergoing Phase I evaluation in both the United States (through the NCI) and United Kingdom (through Cancer Research United Kingdom). This review will focus on design, synthesis and structure activity relationship studies of pyrrolobenzodiazepines as anticancer therapeutics reported since 2003.

Cipolla, L., Araújo, A., Airoldi, C., & Bini, D. (2009). Pyrrolo[2,1-c][1,4]benzodiazepine as a scaffold for the design and synthesis of anti-tumour drugs. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 9, 1-31 [10.2174/187152009787047743].

Pyrrolo[2,1-c][1,4]benzodiazepine as a scaffold for the design and synthesis of anti-tumour drugs

CIPOLLA, LAURA FRANCESCA;AIROLDI, CRISTINA;BINI, DAVIDE
2009

Abstract

Compounds that bind in the minor groove of DNA have found use in the experimental treatment of cancer and certain infectious diseases. Furthermore, agents which target and can recognize discrete sequences of DNA have the potential to offer selective therapies by modulating the activity of specific transcription factors or genes. For this reason, a number of sequence-selective DNA binding agents have been evaluated with a range of affinities and recognition fidelities. In this respect, the pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are of interest as they bind to guanine residues in the minor groove with a preference for Pu-G-Pu sequences. A dramatic increase in cytotoxicity and sequence selectivity has been achieved by linking two PBD units to form PBD dimers as cross-linking agents on opposite DNA strands (e.g., interstrand cross-links). SJG-136 is currently undergoing Phase I evaluation in both the United States (through the NCI) and United Kingdom (through Cancer Research United Kingdom). This review will focus on design, synthesis and structure activity relationship studies of pyrrolobenzodiazepines as anticancer therapeutics reported since 2003.
Articolo in rivista - Articolo scientifico
Scientifica
Anti- Tumour Drugs; Synthesis; pyrrolo[2,1-c][1,4]benzodiazepines (PBDs); transcription factors; cytotoxicity; PBD dimers; anticancer therapeutics
eng
Cipolla, L., Araújo, A., Airoldi, C., & Bini, D. (2009). Pyrrolo[2,1-c][1,4]benzodiazepine as a scaffold for the design and synthesis of anti-tumour drugs. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 9, 1-31 [10.2174/187152009787047743].
Cipolla, L; Araújo, A; Airoldi, C; Bini, D
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/14452
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