Chartreusin and
elsamicin A are structurally related
antibiotics that bind to GC-rich 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
DNA-
elsamicin 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.