Chemotherapeutic compounds, effect

Chemotherapy was first used for the treatment of advanced lymphomas in the 1940s [1], Since then several classes of chemotherapeutic compounds such as alkylating agents, antimetabolites, anthracyclines, plant alkaloids, and later topoisomerase inhibitors and taxanes have been identified or synthesized to treat various forms of cancer [2, 3], Although numerous in vitro and animal studies have demonstrated their effectiveness in inducing cancer cell death (cytotoxic) or cell growth arrest (cytostatic), these promising anticancer activities seen in the controlled environment of the laboratory frequently do not translate well into the expected clinical outcomes [4-8]. 

The sensitivity of luminescence to many substances that cause harmful effects in animals invites preliminary tests for possible nontoxicity of new chemotherapeutic compounds. Unfortunately, the criterion is not... 

Several of the naturally occurring indoles also have clinical importance. The dimeric vinca alkaloid vincristine and closely related compounds were among the first of the anti-mitotic class of chemotherapeutic agents for cancer[14]. The mitomycins[15] and derivatives of ellipticine[16] are other examples of compounds having anti-tumour activity. Reserpine, while not now a major drug, was one of the first compounds to show beneficial effects in treatment of mental disorders[17]... 

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). 

The best example of using this knowledge in drug discovery is the identification of Prostratin. While working in Samoa to identify plants with potential chemotherapeutic properties, Dr. Paul Cox documented the use of Homalanthus nutans for the treatment of hepatitis [16]. Surprisingly, when extracts of this plant were incidentally examined for anti-HIV properties, the extract appeared effective for treatment of HIV [17]. Eventually, this compound was shown to be effective at activating the latently infected T-cell pool [18]. Importantly, this population of cells is a principal reason for HIV persistence [19]. 

Schmidt If you are looking for a compound that is relatively specific for Gl, there is a chemotherapeutic agent being introduced into clinical trials called flavupiridol, which has preferential effects on Gl and leads to degradation of cyclin D1 in breast cancer cells. 

I 10. The answer is a. (Hardman, p 1302J Cyclophosphamide is classified as a poly functional alkylating drug that transfers its alkyl groups to cellular components. The cytotoxic effect of this agent is directly associated with the alkylation of components of DNA. Methotrexate and 5-FU are classified as anti metabolites that block intermediary metabolism to inhibit cell proliferation. Tamoxifen is an antiestrogen compound. Doxorubicin is classified as an antibiotic chemotherapeutic agent. 

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