Anticancer chemotherapeutic drugs

Antineoplastic Drugs. Cyclophosphamide (193) produces antineoplastic effects (see Chemotherapeutics, anticancer) via biochemical conversion to a highly reactive phosphoramide mustard (194) it is chiral owing to the tetrahedral phosphoms atom. The therapeutic index of the (3)-(-)-cyclophosphamide [50-18-0] (193) is twice that of the (+)-enantiomer due to increased antitumor activity the enantiomers are equally toxic (139). The effectiveness of the DNA intercalator dmgs adriamycin [57-22-7] (195) and daunomycin [20830-81-3] (196) is affected by changes in stereochemistry within the aglycon portions of these compounds. Inversion of the carbohydrate C-1 stereocenter provides compounds without activity. The carbohydrate C-4 epimer of adriamycin, epimbicin [56420-45-2] is as potent as its parent molecule, but is significandy less toxic (139). 

A possible source for chemotherapeutic agents is the medicinal flora of the Asia-Pacific region. The purpose of this chapter is to provide a fundamental approach to understanding the potential of the medicinal flora of this region as a source of new anticancer drugs. 

Anticancer drugs act on cells in active proliferation and may interfere with a specific phase of the cell cycle or act independently from it. Some of these drugs are naturally occurring compounds, identified in plants or microorganisms, some are synthetic chemicals. Among the major classes of chemotherapeutics include antimetabolites, alkylating agents, inhibitors of the... 

However, several types of cancer do not respond well to treatment. For example, the majority of metastatic cancers cannot be cured by current chemotherapeutic methods or by any other type of treatment.11 In addition, some of the most common forms of adult neoplastic disease are difficult to treat by using anticancer drugs. As indicated in Table 36-9, the number of deaths associated with colorectal, prostate, and breast cancer is unacceptably high, and the mortality rate for lung cancer and pancreatic cancer is well over 90 percent in both men and women. 

Cancers can become resistant to drugs through several different mechanisms. One common mechanism occurs when the cancer cell synthesizes a glycoprotein that acts as a drug efflux pump.15,74 The glycoprotein pump is inserted into the cancer cell s membrane and effectively expels different types of anticancer drugs from the cancer cell. Thus, cancer chemotherapeutic agents are ineffective because they are removed from the cell before they have a chance to exert cytotoxic effects. 

Cisplatin [SIS pla tin] is a member of the platinum coordination complex class of anticancer drugs. Because of cisplatin s severe toxicity, carboplatin [KAR bow pla tin] was developed. The therapeutic effectiveness of the two drugs is similar but their pharmacokinetics, patterns of distribution and dose-limiting toxicities differ. Cisplatin has synergistic cytotoxicity with radiation and other chemotherapeutic agents. 

Diacetoxyscirpenol (DAS), also called anguidine, was evaluated as a potential chemotherapeutic agent for cancer treatment (reviewed by Jarvis and Acierto, 1989). While the therapeutic efficacy was insufficient to develop DAS as an anticancer drug, valuable information was obtained in the... 

Schrijvers D, Highley M, De Bruyn E, Van Oosterom AT, Vermorken JB. Role of red blood cells in pharmacokinetics of chemotherapeutic agents. Anticancer Drugs 1999 10 147-53. 

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