Cancer chemotherapy natural products

Epothilones A, B and E (4,5 and 6) (Fig. 2) are representative members of a new class of bacterially derived natural products which exhibit potent biological activity. Isolated by Hofle and coworkers [6] from a soil sample collected near the Zambesi river, the compounds have provided a great deal of excitement in the scientific community due to their potent cytotoxicity against a number of multiple drug-resistant tumor cell lines and because of the mechanism by which they exert this effect. Like Taxol [7], the epothilones promote the combination of a- and 3-tubulin subunits and stabilize the resulting microtubule structures. This mode of action inhibits the cell division process and is, therefore, an attractive strategy for cancer chemotherapy [7,8]. 

Newman DJ, Cragg GM, Holbeck S, Sausville EA, Natural products and derivatives as leads to cell cycle pathway targets in cancer chemotherapy, Curr Cancer Drug Targets 2 279-308, 2002. 

Table 54-4 Natural Product Cancer Chemotherapy Drugs Clinical Activity and Toxicities. ...

Prevention of Cancer Chemotherapy Drug-Induced Adverse Reaction, Antitumor and Antimetastatic Activities by Natural Products... 

Taxol is a natural product that has impacted the lives of hundreds of thousands of people. Since 1992, it has been the API in certain chemotherapy agents provided to patients suffering from a variety of cancers and is approved for the treatment of ovarian, breast, non-smaU-ceU lung cancers and AIDS-related Kaposi s sarcoma in over 50 countries. 

Another area in which natural products have had a major impact on longevity and quality of life is in the chemotherapy of cancer (see Chapter 62). In fact, most major anticancer drugs are derived from plants or microorganisms. Important examples include bleomycin, doxorubicin, daunorubicin, vincristine, vinblastine, mitomycin, streptozocin, and most recently, paclitaxel... 

The camptothecins are natural products that are derived from the Camptotheca acuminata tree, and they inhibit the activity of topoisomerase I, the key enzyme responsible for cutting and religating single DNA strands. Inhibition of the enzyme results in DNA damage. Topotecan is indicated in the treatment of patients with advanced ovarian cancer who have failed platinum-based chemotherapy and is also approved as second-line therapy of small cell lung cancer. The main route of elimination is renal excretion, and for this reason caution must be exercised in patients with abnormal renal function, with dosage reduction being required. 

Historically, anticancer drugs have been discovered through large-scale screening of synthetic chemicals and natural products against animal tumor systems. The drugs discovered in the first two decades of cancer chemotherapy (1950-1970) primarily... 

A recurring liability of natural products, at least in the area of cancer chemotherapy, is that although many are generally very potent, they have limited solubility in aqueous solvents and exhibit narrow therapeutic indices. These factors have resulted in the demise of a number of promising leads, such as bruceantin and maytansine. 

Prevention by Natural Products and Foodstuffs of Side Effects Induced by Cancer Chemotherapy Drug without Loss of Antitumor Activity. 

Butenolides constitute a major class of lactone natural products which have been shown to play important roles in cancer chemotherapy [75]. It was previously noted that introduction of a double bond in conjugation with the lactone carbonyl results in shielding of the carbonyl NMR chemical shift for example compare the carbonyl chemical shift of 44 and 48 [74]. However,... 

---