Cytostatic agent

The unsaturated substituent in the carbene complex 1 often is aromatic or heteroaromatic, but can also be olefinic. The reaction conditions of the Dotz procedure are mild various functional groups are tolerated. Yields are often high. The use of chromium hexacarbonyl is disadvantageous, since this compound is considered to be carcinogenic however to date it cannot be replaced by a less toxic compound. Of particular interest is the benzo-anellation procedure for the synthesis of anthra-cyclinones, which are potentially cytostatic agents. ... 

Erythropoietin (Eprex ) is physiologically produced in the kidney and regulates proliferation of committed progenitors of red blood cells. It is used to substitute erythropoietin in severe anemias due to end stage renal disease or treatment of cancer with cytostatic agents. Side effects include hypertension and increased risk of thrombosis. 

In view of the importance of the motor dynein for microtubular function, this protein is currently considered as a new target for the development of cytostatic agents. 

Sculier, J. P., Coune, A., Brassine, C., Laduron, C., Atassi, G., Ruysschaert, J. M., and Fruhling, H. (1986). Intravenous infusion of high doses of liposomes containing NSC 251635, a water-insoluble cytostatic agent. A pilot study with pharmacokinetic data, J. Clin. Oncol., 4, 789-797. 

Cisplatin is a platinum complex (platinum dichloride and two ammonia molecules) used as a cytostatic agent against cancer. The molecule cross-links DNA strands, thus leading to cell death. 

Since glutathione reductase is a cornerstone of the malaria parasite antioxidant defence and repair mechanism, it is a potential target for antimalarial and cytostatic agents. 

Keywords Immunochemical techniques Antibiotics Steroid hormones Analgesics Cytostatic agents... 

Considering all aspects, sex hormones, antibacterials, and antineoplastic agents were identified by Christensen as the three most relevant groups of chemicals concerning their potential human risk as a consequence of drug exposure via the environment [10]. Immunochemical methods for hormones and antibiotics have already been discussed above. In this section we will describe methods based on the use of antibodies for the analysis of analgesics, NSAIDs, and cytostatic agents. 

Table 8 Some representative immunochemical techniques developed for the detection of analgesics, NSAIDs, and cytostatic agents... 

Few examples of immunochemical methods for cytostatic agents have been reported (Table 8). Within the context of work performed by Aherne et al. [33], on the use of immunochemical methods in the analysis of microcontaminants in water samples, was reported the use of a RIA for the detection of methotrexate with a LOD of 6.25 ng mL-1. With the exception of a hospital effluent (concentration of 1 ng mL 1 of methotrexate was found), all samples (river and potable water) were negative. 

Other drugs can cause hypercalcaemia and increase the risk of forming kidney stones that can damage the kidneys and ureters and cause infections. Examples are cytostatic agents, sulphonamides, radiological contrast media, statins (through rhabdomyolysis), vitamin D and intake of calcium and antacids. 

Several dihydropyridazinones of type (78, R1 = cycloamino R2 = H, cycloamino R3 = H, Ph) characterized by a cycloaminomethyl substituent at C-5 have been reported to exhibit cytostatic activity [284, 285], In addition, compounds having a pyridazinone or pyridazinedione moiety linked to the purine system by a sulphur atom (79) have been prepared as potential cytostatic agents [286]. 

Frmctional imaging such as PET scanning and SPECT scanning is also likely to be explored for detecting early activity of these cytostatic agents just as PET scanning documented the early activity of Gleevec in patients with G1 stromal tumors. ... 

Most studies were performed with hyperosmolar solutions. Hypertonic disruption is under clinical evaluation for enhanced delivery of small molecular weight cytostatic agents to brain tumours. Technically, the procedure is performed as a high-flow short-term infusion of 25% mannitol or arabinose under general anaesthesia. The underlying mechanism is a sequelae of endothehal cell shrinkage, disruption of tight junctions and vasodilatation by osmotic shift [72]. 

Substances known as intercalators, such as rifamycin and actinomycin D (bottom) are deposited in the DNA double helix and thereby interfere with replication and transcription (B). As DNA is the same in all cells, intercalating antibiotics are also toxic for eukaryotes, however. They are therefore only used as cytostatic agents (see p. 402). Synthetic inhibitors of DNA topoisomerase II (see p. 240), known as gyrase inhibitors (center), restrict replication and thus bacterial reproduction. 

Most cytostatic agents directly or indirectly inhibit DNA replication in the S phase of the cell cycle (see p. 394). The first group (A) lead to chemical changes in cellular DNA that impede transcription and replication. A second group of cytostatic agents (B) inhibit the synthesis of DNA precursors. 

Dihydrofolate reductase acts as an auxiliary enzyme for thymidylate synthase. It is involved in the regeneration of the coenzyme N, N -methylene-THF, initially reducing DHF to THF with NADPH as the reductant (see p. 418). The folic acid analogue methotrexate, a frequently used cytostatic agent, is an extremely effective competitive inhibitor of dihydrofolate reductase. It leads to the depletion of N, N -methylene-THF in the cells and thus to cessation of DNA synthesis. 

To reduce the side effects of cytostatic agents, new approaches are currently being developed on the basis of gene therapy (see p. 264). Attempts are being made, for example, to administer drugs in the form of precursors (known as prodrugs), which only become active in the tumor itself ( tumor targeting ). 

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