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7) Antibiotics:
A number of antibiotics such as anthracyclines, dactinomycin,
bleomycin, adriamycin, mithramycin, bind to DNA and inactivate
it. Thus the synthesis of RNA is prevented.
General properties of these drugs include: interaction with
DNA in a variety of different ways including intercalation (squeezing
between the base pairs), DNA strand breakage and inhibition with
the enzyme topoisomerase II. Most of these compounds have been
isolated from natural sources and antibiotics. However, they
lack the specificity of the antimicrobial antibiotics and thus
produce significant toxicity.
The anthracyclines are among the most important antitumor
drugs available. Doxorubicin is widely used for the treatment
of several solid
tumors while daunorubicin and idarubicin are used exclusively
for the treatment of leukemia.
These agents have a number of important effects including:
intercalating (squeezing between the base pairs) with DNA affecting
many functions of the DNA including DNA and RNA synthesis. Breakage
of the DNA strand can also occur by inhibition of the enzyme
topoisomerase II.
Doxorubicin - Chime
in new window
Daunorubicin - Chime
in new window
Dactinomycin (Actinomycin D):
At low concentrations dactinomycin inhibits DNA directed RNA
synthesis and at higher concentrations DNA synthesis is also
inhibited. All types of RNA are affected, but ribosomal RNA is
more sensitive. Dactinomycin binds to double stranded DNA , permitting
RNA chain initiation but blocking chain elongation. Binding to
the DNA depends on the presence of guanine.
Actinomycin D - Chime
in new window
Link to Chime: Actinomycin
- details of structure
Link to Chime: Actinomycin
with DNA
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