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- Camptothecin (CPT) is a cytotoxic
quinoline alkaloid which inhibits the DNA enzyme topoiso- merase I (topo
- It was discovered in 1966 by M. E.
Wall and M. C. Wani in systematic screening of natural products for
- Camptothecin was isolated from the
bark and stem of Camptotheca acuminata (Camptotheca, Happy tree), a tree
native to China.
- CPT showed remarkable anticancer
activity in preliminary clinical trials but also low solubility and
(high) adverse drug
- Camptothecins (CPT) are one of the
most important alkaloids of the 21st century because of their clinical
against cancer and HIV-I.
- Camptothecin, a
pentacyclic quinoline alkaloid, has been discovered through an extensive
screening by the U.S. National Cancer Institute. This compound exhibits
an antitumor activity due to its inhibitory action to DNA topoisomerase
destroys the cancerous cells and prevents the further division of these
cells, they also induce the self-destruction of these cancerous cells,
this mode of cancer treatment is cell specific and destroys only those
affected cancerous cells.
- CPT has a unique penta- cyclic ring
structure which gives itself and its
derivatives the necessary antitumour activity and such spatial
cannot be synthesized artificially.
- CPT inhibits the replica-tion of
Deficiency Virus (HIV) in vitro and is also shown to be effective in the
complete remission of lung, breast, uterine and cervical cancer. The
molecular and cytotoxic effects of camptothecin on Plasmodium falciparum proven that it is an interesting target for new
anti-malarial drug development.
- Camptothecin affects the activity of
the enzyme topoisomerase I, whose normal action is to cleave, unwind,
and religate DNA. When camptothe- cin binds to topoiso- merase I, it
will be able to cleave but not to religate DNA. Thereby, camptothecin
causes single strand breaks in DNA.
- Camptothecins are among the most
recently approved anticancer agents with two
derivatives approved by the FDA: Camptosar (Irinotecan hydrochloride;
CPT-11) for advanced colo-rectal carcinomas and Hycamtin(Topotecan) for
ovarian cancers. Both drugs are water-soluble derivatives of the parent
natural alkaloid camptothecin.
- Camptothecin (CPT) has recently
attracted increasing attention as a promising anticancer agent for a
variety of tumors. But the clinical application is largely hampered by
its extreme water insolubility and unpredictable side effect. It is
essential to establish an efficient and safe protocol for the
admi-nistration of CPT versus melanoma.
- Camptothecins are an
important and fast growing class of anti-cancer drugs. However, like
taxanes, their full benefit is limited by poor solubility and
- At present,
semisynthetic water-soluble camptothe- cin analogs, topotecan and
irinotecan, are prescribed as clinical antitumor drugs through out the
world. The worldwide market size of irinotecan / topotecan in 2003 was
estimated at about US$1 billion. Worldwide sales for camptothecins
exceeded $725.0 million in 2004.
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