Inhibition of cell division

The growth inhibitory mechanism of the thiocarbamate herbicides, eg, EPTC, butylate, cycloate, diaHate, and triaHate, is not well defined. Cell elongation, rather than cell division, appears to be inhibited (183), although mitotic entry may be inhibited by diaHate (184). Thiocarbamates have a greater effect on shoot than toot tissue (163,184). The weU-documented inhibition of Hpid synthesis by thiocarbamates certainly contributes to the observed inhibitions of cell division and elongation. These compounds may also inhibit gibbereUic acid synthesis (185). 

Although most /3- lactam antibiotics bind covalently to some or all of the same six proteins, there are decided differences among them in terms of their relative affinities. For example, cefoxitin (see Table 1 for structures) fails to bind to protein 2 while cephacetrile binds very slowly to proteins 5 and 6. Cephaloridine binds most avidly to protein 1, the transpeptidase, and inhibits cell elongation and causes lysis at its minimum inhibitory concentration. On the other hand, cephalexin binds preferentially to protein 3 and causes inhibition of cell division and filament formation (75PNA2999, 77MI51002). 

Variation in the magnesium (Mg) content of the medium may exert a marked effect on cell division of some bacteria. In a Mg-deficient medium, Gram-positive rods grow in the form of long filaments. Such filaments revert to normal forms when transferred to the same medium supplemented with suitable concentrations of Mg. Filament formation is enhanced by the addition of zinc and cobalt. Inhibition of cell division occurs also in media supplemented with an excess of Mg. 

Mehendale HM, Ray SD. 1990. Inhibition of cell division in hepatoma cell cultures by chlordecone and carbon tetrachloride combination. Toxicology in Vitro 4(3) 179-183. 

Khattar, M. M. Overexpression of the hslVU operon suppresses SOS-mediated inhibition of cell division in Escherichia coli. FEBS Lett. 1997, 414, 402-404. 

Rosenberg B, VanCamp L, Krigas T. Inhibition of cell division in Escherichia coli by electrolysis products from platinum electrode. Nature 1965 205 698-699. 

Growth Inhibit growth (pharmacologic doses) Inhibition of cell division and DNA synthesis... 

Reznikoff, C.A., Bertram, J.S., Brankow, D.W., and Heidelberger, C. (1973) Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of cell division, Cancer Res. 33,3230. 

Azathioprine is a cytotoxic inhibitor of purine synthesis effective for the control of tissue rejection in organ transplantation. It is also used in the treatment of autoimmune diseases. Its biologically active metabolite, mercaptopurine, is an inhibitor of DNA synthesis. Mercaptopurine undergoes further metabolism to the active antitumour and immunosuppressive thioinosinic acid. This inhibits the conversion of purines to the corresponding phosphoribosyl-5 phosphates and hypoxanthine to inosinic acid, leading to inhibition of cell division and this is the mechanism of the immunosuppression by azathioprine and mercaptopurine. Humans are more sensitive than other species to the toxic effects of the thiopurines, in particular those involving the haematopoietic system. The major limiting toxicity of the thiopurines is bone marrow suppression, with leucopenia and thrombocytopenia. Liver toxicity is another common toxic effect. 

K3 Inhibition of cell division Chloroacetanilides Carbamates Acetamides Benzamides Oxyacetamides 15... 

The molecular basis for the therapeutic effects of the purine analogs is unknown. Intracellular 6-thioguanine causes inhibition of purine nucleotide metabolism and DNA synthesis and repair, resulting in inhibition of cell division and proliferation. 

Using antibiotics in a concentration of 0.1 mM, a 2-5 times elongation of the cell length was observed due to inhibition of cell division. The fibers became 1-2 times wider compared to common BC. Because of the better uni-planar orientation of the wider fibers after pressing of the membranes, the Young s modulus of this material increases by up to 34-42%. 

Modes of action of allelochemicals are diverse and have been described for isolated compounds, as well as for mixtures. They can affect various physiological processes, such as disruption of membrane permeability,22 ion uptake,28 inhibition of electron transport in photosynthesis and respiratory chain,1,10,33 alterations of some enzymatic activities, 1 and inhibition of cell division, 1 among others. 

Inhibition of cell division, lack of spindle formation, inhibition of protein synthesis, increased cell size, radial elongation of cells, polyploid nuclei chromosome contraction, cell wall thickening. 

While for the pyrrole derived lamellarins and related compounds no activity has been described, several pentacyclic lamellarins show important cytotoxic activities. Lamellarin D at a concentration of 19 pg/ml caused a 78% inhibition of cell division in the fertilized sea urchin egg assay while lamellarin C caused 15% inhibition but lamellarins A and B were inactive <85JA5492>. Lamellarins I, K and L present significant cytotoxicity against P338 and A549 cultured cell lines and lamellarins K and L also exhibit immunomodulatory activity <93AJC489>. 

Rathbuniosides Ri (15) and R2 (16) as well as six related diglycosides (Structures 17-22, Fig. (7) and (8)) isolated from the starfishes Mediaster murrayi [37], Ceramaster patagonicus [38] and Culcita novaeguineae [39] showed inhibition of cell division of the fertilized eggs of the sea urchin Strongylocentrotus intermedins as well as hemolytic activity [40]. 

Thiophanate methyl (74) is, like thiabendazole (54), a member of the benzimidazole group of fungicides since it is metabolised in vivo to carbendazim (83), which is the active entity. Thiophanate methyl is synthesised by condensation of o-phenylenediamine (82) with potassium thiocyanate and methyl chloroformate (Scheme 17). The benzimidazoles owe their fungicidal action to the inhibition of cell division in the fungus due to interference with the microtubular assembly. 

The toxicity threshold for Scenedesmus quadricauda (green algae) is >10000mgH. Toxic effect is multiplication inhibition of cell division. Toxicity threshold for Entosiphon sulcatum (protozoa) is > 29 mg 1 and the toxic effect is inhibition of cell multiplication. 

Vinca alkaloids (vincristine, vinblastine, vinorelbine) are derived from the periwinkle plant (Vinca rosea). These agents work by binding to tubulin at a site different than colchicine or paclitaxel. They block polymerization, which prevents the formation of the mitotic spindle, and are used as antineoplastic agents. Taxanes produce a stabilization of microtubules similar to colchicine, but by a different mechanism, and also halt cells in metaphase. Paclitaxel (taxol) is the taxane used clinically. It is derived from the bark of the pacific yew. Taxol disrupts several microtubule-based functions as completely as inhibitors of polymerization, emphasizing the importance of assembly/disassembly balance in microtubule function. Recently, it has been found that paclitaxel also binds to and inhibits the function of a protein called bcl-2, an inhibitor of one or more pathways involved in mediating apoptosis. PaclitaxeTs interference with this function promotes apoptosis in addition to its microtubule-related inhibition of cell division. 

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