Alkylating antineoplastics

Table 4-3. Currently Used Alkylating Antineoplastic Drugs...

The drug essentially cross-links DNA and, therefore, behaves like alkylating antineoplastic agents. In general, the platinum complex acts as apotent inhibitor of DNA polymerase. Based on adequate... 

Ornithine decarboxylase is a pyridoxal dependent enzyme. In its catalytic cycle, it normally converts ornithine (7) to putrisine by decarboxylation. If it starts the process with eflornithine instead, the key imine anion (11) produced by decarboxylation can either alkylate the enzyme directly by displacement of either fluorine atom or it can eject a fluorine atom to produce viny-logue 12 which can alkylate the enzyme by conjugate addidon. In either case, 13 results in which the active site of the enzyme is alkylated and unable to continue processing substrate. The net result is a downturn in the synthesis of cellular polyamine production and a decrease in growth rate. Eflornithine is described as being useful in the treatment of benign prostatic hyperplasia, as an antiprotozoal or an antineoplastic substance [3,4]. 

Alkylating Agents. Figure 4 Chemical structure of some platinum antineoplastic drugs. 

Bendamustine is a useful antineoplastic drug for the treatment of non-Hodgkin s lymphomas, multiple myeloma and as a partner drug in the combination therapy of some solid tumors. The cross-resistance with other alkylating drugs is not complete. Myelosuppression and lymphocytopenia is its main dose-limiting toxicity. 

Cancer, Molecular Mechanism of Therapy Antineoplastic Agents Alkylating Agents Antimetabolites... 

The antineoplastic antibiotics, unlike their anti-infection antibiotic relatives, do not have anti-infective (against infection) abilily. Their action is similar to the alkylating dragp. Antineoplastic antibiotics appear to interfere with DNA and RNA synthesis and therefore delay or inhibit cell division, including the reproducing ability of malignant cells. Examples of antineoplastic antibiotics include bleomycin (Blenoxane), doxorubicin (Adriamycin), and plicamycin (Mithracin). 

The following sections give selected interactions of die alkylating dragp, antimetabolites, antibiotics, hormones, miotic inhibitors, and miscellaneous antineoplastic dragp. The nurse should consult appropriate sources for a more complete listing of interactions before any antineoplastic drug is administered. 

Lin, A. J. Shansky, C. W. Sartorelli, A. C. Potential bioreductive alkylating agents. 3. Synthesis and antineoplastic activity of acetoxymethyl and corresponding ethyl carbamate derivatives of benzoquinones. J. Med. Chem. 1974, 17, 558-561. 

Capecitabine is an antimetabolite neoplastic and cyclophosphamide is an alkylating neoplastic, both of which can be administered orally. Carboplatin is a platinum compound (antineoplastic). All currently available platinum compounds are administered parenterally via the intravenous route. 

Cyclophosphamide is an antineoplastic agent that causes DNA cross-linking and abnormal base-pairing through a mechanism called alkylation, hence the name alkylating agent. Cyclophosphamide may also be used in resistant rheumatoid arthritis. 

Alkyl halides, alkyl sulfonates and other alkylating agents have also been subject to scmtiny in spheres other than pharmaceuticals, such as in environmental analysis. Various approaches have included two-step SPE, derivatisation with trifluoroacetic anhydride followed by GC/MS (for cyclophosphamide and its analogues in sewage water) SPE on surface water to isolate the antineoplastic agents carmustine, chlorambucil, cyclophosphamide and melphalan for LC-UV and LC-fluorescence measurements and derivatisation of alkyl halides and epoxides with 4-nitrothiophenol followed by HPLC-UV detection (claimed to be better than NBP derivatisation). A patent exists for a field test kit for mustard gases in military use based on NBP derivatisation. 

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