Cytotoxic substance

Rat macrophages activated by endotoxin in vitro released a factor cytotoxic for sarcoma cells but not for normal cells (Currie and Basham 1975). 

A receptor is an integral membrane protein which transduces biological information, conferred in signals. 

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Leptosins D-F (258a-c, Scheme 39) [94JCS(P1)1859] were isolated by Takahashi and co-workers from the culture of a strain of Leptosphaeria sp. as cytotoxic substances against the P388 lymphocytic leukemia cell line comparable to that of mitomycin C. Utilizing the nucleophilic substitution reaction of 1-hydroxytryptamines, a simple methodology for the synthesis of core structures of leptosins has been developed (2000H1255). 

This reaction has been used in coupling two fragments in a synthesis of leucascan-drolide, a cytotoxic substance isolated from a sponge.49... 

A massive body of evidence has already been presented clearly indicating that the medicinal plants of the Pacific Rim elaborate a broad array of cytotoxic substances. Most of these have been characterized using experimental procedures designed to examine the cytotoxicity of natural products against human tumor cell lines. These procedures involve in vitro screening where the viability of cultured cells after exposure to an extract or a purified substance is measured. 

Colloidal gold-labeled (strept)avidin can be used as highly sensitive detection reagents for microscopy techniques (Cubie and Norval, 1989) (Chapter 24). Finally, cytotoxic substances coupled to (strept)avidin can be used to direct cell-killing activity toward a tumor-cell-bound, biotinylated monoclonal antibody (or other targeting molecule) for cancer therapy (Hashimoto et al, 1984) (Chapter 21). 

Recent studies, including the use of Microtox and ToxAlert test kits [55,56], were carried out for the determination of the toxicity of some non-ionic surfactants and other compounds (aromatic hydrocarbons, endocrine disruptors) before implementation on raw and treated wastewater, followed by the identification and quantification of polar organic cytotoxic substances for samples with more than 20% inhibition. Furthermore, the study of their contribution to the total toxicity was obtained using sequential solid-phase extraction (SSPE) before liquid chromatography-mass spectrometry (LC-MS) detection. This combined procedure allows one to focus only on samples containing toxic substances. 

Presumably, any cytotoxic substance that destroys bone marrow and lymphoid tissue may be used as an immunosuppressant. Among these drugs, the most widely used primarily for autoimmune diseases are vincristine, methotrexate, and cytarabine. However, their use should be considered experimental. Only methotrexate is seriously and sufficiently recognized as an initial drug for treating rheumatoid arthritis. 

Sea-Originated Cytotoxic Substances Norihito Maru and Daisuke Uemura1 ... 

Amagata T, Usami Y, Minoura K, Ito T, Numata A (1998) Cytotoxic Substances Produced by a Fungal Strain from a Sponge Physico-Chemical Properties and Structures. J Antibiot 51 33... 

Takahashi A, Agatsuma T, Ohta T, Nunozawa T, Endo T, Nozoe S (1993) Russuphelins B, C, D, E and F, New Cytotoxic Substances from the Mushroom Russula subnigricans HONGO. Chem Pharm Bull 41 1726... 

The in vivo metabolism of capecitabine (1) to the active tumor cytotoxic substance 5-fluorouracil (5) is now fairly well understood. When capecitabine is administered orally it is delivered to the small intestine, where it is not a substrate for thymidine phosphorylase in intestinal tissue, and so passes through the intestinal mucosa as an intact molecule and into the bloodstream. When 1 reaches the liver, the carbamate moiety is hydrolyzed through the action of carboxylesterase enzymes, liberating 5 -deoxy-5-fluorocytidine (5 -DFCR, 10). DFUR is partially stable in systemic circulation, but eventually diffuses into tumor cell tissue where it is transformed into 5 -deoxy-5-fluorouridine (5 -DFUR, 9) by cytidine deaminase, an enzyme present in high concentrations in various types of human cancers compared to adjacent healthy cells (although it is present in significantly lower levels in the liver). Within the tumor, 5-... 

A new cytotoxic substance named mechercharmycin A 164, and its linear congener mechercharmycin B 165 were isolated from marine-derived Thermoactinomyces sp. YM3-25l/ 164 exhibited relatively strong antitumor activity, whereas 165 exhibited almost no such activity. 

Anticancer chemotherapies Azathioprine, cyclophosphamide, methotrexate etc. The cytotoxic substances affect proliferating cells and hematopoiesis as well as lymphocyte proliferation are especially sensitive. Association with risk of clinical infections clearly established. 1 % of chemotherapy patients develop an independent cancer within 10 years, 3 % within 20. Noteworthy, some anticancer drugs are now used also as immunosuppressant for autoimmune diseases... 

A number of S. aureus strains produce a several cytotoxic substances, including the hemolysins alpha, beta and delta. 

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