Current Medicinal Chemistry-Anti-Cancer Agents

Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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Chartreusin, Elsamicin A and Related Anti-Cancer Antibiotics

Author(s): Jose Portugal.

Abstract:

Chartreusin and elsamicin A are structurally related antibiotics that bind to GCrich tracts in DNA, with a clear preference for B-DNA over Z-DNA. They inhibit RNA synthesis and cause single-strand scission of DNA via the formation of free radicals. Elsamicin A can also be regarded as the most potent inhibitor of topoisomerase II reported so far. It can inhibit the formation of several DNA-protein complexes. Elsamicin A binding to the P1 and P2 promoter regions of the c-myc oncogene inhibits the binding of the Sp1 transcription factor, thus inhibiting transcription. Despite the pharmacological interest in chartreusin, elsamicin A and their derivatives, there is no experimental data on the structure of their complexes with DNA. This shortcoming has been partially solved by a theoretical approach, which provided some details about the DNAelsamicin A interaction, and the thermodynamic characterization of the binding of chartreusin and elsamicin A to DNA. Elsamicin A but not chartreusin is being developed clinically as an anti-cancer agent. IST-622 (6-O-(3- ethoxypropylonyl)-3,4-O-exo-benzylidene-chartreusin), a novel semi-synthetic derivative of chartreusin, which has shown a promising anti-cancer activity in a phase II study, appears to be a pro-drug with a more suitable pharmacokinetic profile than chartreusin.

Keywords: dna-binding drugs, chartreusin, elsamicin a, intercalation

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Article Details

VOLUME: 3
ISSUE: 6
Page: [411 - 420]
Pages: 10
DOI: 10.2174/1568011033482215
Price: $58