Antineoplastic effects

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). 

Decitabine (5-aza-deoxycytosine) is an analog of the nucleoside 2 -deoxycytidine. It is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and by inhibition of the enzyme DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. DNA hypomethylation is achieved at concentrations below those required to significantly inhibit DNA synthesis, which may promote restoration of function to genes associated with control of cellular differentiation and proliferation. Cytotoxicity in rapidly dividing cells may also result from covalent adducts between DNA methyltransferase and decitabine. 

Bicalutamide may increase the effect of oral anticoagulants. Flutamide enhances the action of leuprolide. Additive antineoplastic effects may occur when leuprolide is administered with megestrol or flutamide. Estrogens decrease the effectiveness of tamoxifen. 

Ideally, future antineoplastic drug discovery should be based on a more rational, botanical, chemical, and pharmacological approach. A possible way to test the antineoplastic effects of compounds would be to use some semi in vitro-in vivo models. A more rational approach in antineoplastic research, combined with the enormous chemodiversity of flowering plants, will lead to the discovery of several molecules of clinical value. 

WANG, W., ZHOU, J., XU, L., ZHEN, Y., Antineoplastic effect of intracellular expression of a single-chain antibody directed against type IV collagenase, J. Environ. Pathol. Toxicol. Oncol, 2000,19, 61-68. 

Different strains of Streptomyces produce several substances that exhibit quinoid stmcture and have been shown to exert antibiotic and antineoplastic effects in pre-chnical tests. The largest group of these compounds is the anthracychnes, which are used extensively in the treatment of several... 

Nagai, K. and Suda, T. (1986). Antineoplastic effects of carnosine and beta-alanine—Physiological considerations of its antineoplastic effects. Nippon Seirigaku Zasshi 48, 741-747. 

The biosynthesis 237,5381 involves enzymatic dehydration of serine and threonine residues in a manner similar to the formation of thiazoles and dihydrothiazoles vide supra) with or without subsequent oxidation to yield the 2-(l-aminoalkyl)oxazole-4-carboxylic acid and 2-(l-aminoalkyl)dihydrooxazole-4-carboxylic acid shown in Scheme 38. These cyclic peptides display interesting physiological properties such as cytotoxicity/541, 569,5831 antitumor activities, or antineoplastic effects/523,5291 but as for the sulfur-containing compounds the mechanism of action is not yet understood despite extensive SAR studies. 515,521,540,5431... 

Rhazya stricta is a poisonous plant used as a traditional folk medicine in the United Arab Emirates. It has possible antineoplastic effects and may have considerable cytotoxicity. Although antidepressant activity has been suggested on the basis of animal studies ( 251), essentially no information on its pharmacology, efficacy, or safety in humans is available. 

Likewise, several drugs working together may increase the antineoplastic effects of one another through a synergistic cytotoxic effect.11... 

Ginseng extracts exert antineoplastic effects and have cytotoxic properties and growth inhibitory properties in vivo. 

Evidence is accumulating that vanadium interferes with the proper functioning of the cell cytoskeleton, which could also be involved in its antineoplastic effects. Taxol, a very successful chemotherapeutic drug, inhibits the function of microtubules in the cytoskeleton. In hepatomoa Morris 5123 cells, V(III) complexed with cysteine and derivatives inhibited the growth of these tumor cells and participated in the rearrangement of actin cytoskeleton architecture [166],... 

Vanadium compounds have an inhibitory effect against induced rat hepatocar-cinogenesis by limiting cell proliferation and chromosomal aberrations in the pre-neoplastic stages of the development of this cancer [169], These antineoplastic effects of vanadium could be related to the induction of apoptosis and selective DNA damage in tumor cells [170], Vanadate has also proven effective against induction of colon carcinomas [171]. A vanadium(III) cysteine compound has been shown to... 

Wilisch A, Haussermann K, Noller A, et al. MDR modulating and antineoplastic effects of B859-035, the (—)isomer of niguldipine. J Cancer Res Clin Oncol 1991 117 S110. 

The patient s symptoms are most likely due to her vincristine therapy. Vinca alkaloids exert antineoplastic effects by binding to tubulin and thereby inhibiting assembly of microtubules. This results in the dissolution of the mitotic spindle apparatus, and cell arrest occurs in the mitosis (M) phase of the cell cycle. Vinca alkaloids are used for a variety of hematologic malignancies and solid tumors, such as lung, testicular, and breast cancers. The most common vinca alkaloids include vincristine, vinblastine, and vinorelbine. 

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