Antimitotic drug

A new antitumor drug, taxol, has been isolated from the bark of Taxus brevifolia, the Pacific yew tree. Like vinblastine and colchicine, taxol inhibits cell replication by acting on microtubules. Unlike these other antimitotic drugs, however, taxol stimulates microtubule polymerization and stabilizes microtubules. 

Colchicine is an antimitotic drug that is highly effective in relieving acute gout attacks but has a low benefit-toxicity ratio. When colchicine is started within the first 24 hours of an acute attack, about two-thirds of patients respond within several hours. The likelihood of success decreases substantially if treatment is delayed longer than 48 hours after symptom onset. 

Emanuel SL, Chamberlin HA, Cohen D (1999) Antimitotic drugs cause increased tumorigenidty of multidrug resistant cells. Int J Oncol 14 487-494 Emoto Y, Manome Y, Meinhardt G, Kisaki H, Kharbanda S, Robertson M, Ghayur T, Wong WW, Kamen R, Weichsdbaum R, Kufe D (1995) Proteolytic activation of protein kinase C delta by an ICE like protease in apoptotic cells. EMBO J 14 6148-6156... 

Figure 4.48 Antimitotic drugs derived from Vinca dimer alkaloids.

Condylox is the brand name of podofilox, an antimitotic drug that can be chemically synthesized or purified from the plant families Coniferae and Berberidaceae (e.g., species of Juniperus and Podophyllum). Condylox 0.5% solu-... 

Alkaloids are nitrogen-based compounds frequently found in plants. Plant alkaloids that are used in treating cancer in humans include traditional agents, such as vincristine and vinblastine, and newer agents, such as vinorelbine, paclitaxel, and docetaxel (Table 36-4). These agents are also known as antimitotic drugs be-... 

David-Pfeuty, T., Simon, C., and Pantaloni, D. (1979). Effect of antimitotic drugs on tubulin GTPase activity and self-assembly./ Biol. Chem. 254, 11696-11702. 

Vinblastine (6.73) is an antimitotic drug that prevents polymerization of tubulin (Figure 6.26). When incubated with tubulin, vinblastine complexes in a 1 1 ratio with tubulin proteins. By blocking polymerization, vinblastine prevents microtubule formation and therefore mitosis. In contrast, paclitaxel (Taxol, 6.74) and epothilone B (6.75) stabilize aggregated tubulin. As a result, in the presence of paclitaxel and epothilone B, cells form static bundles of microtubules that are nonfunctional. Vinblastine and paclitaxel are both approved for clinical use against cancer. Ixabepilone (6.76), an analogue of epothilone B (6.75), has been approved by the FDA for treatment of certain forms of breast cancer. The European Medicines Agency (EMEA) did not approve ixabepilone out of concern over severe side effects.27... 

Antimitotic drugs that target microtubules (MT) or its constituent protein tubulin are one of the most successful classes of anticancer agents discovered so far. MT are long, filamentous, tube-shaped protein polymers that are essential in all eukaryotic cells. Antimitotic agents are compounds that arrest cells in mitosis, which results in the slowing or blocking of mitosis and induction of apoptotic cell death. 

In addition, docking the EC-derived near-atomic resolution structures of tubulin into cryoelectron microscopy maps of MT, has provided more precise insights into the structure of MT, their polymerization dynamics and the way how normal MT behavior is disrupted by antimitotic drugs [23, 24],... 

TEM (triethylenemelamine) Myleran or Busulfan (methanesulfonic acid, tetramethylene ester), antimitotic drugs such as Dichloren (me-chlorethamine hydrochloride) and Cytoxan (cyclophosphamide). X-rays, and steroid therapy show different effects without consistent results. The question must be further investigated. 

Fluorouracil Topical antimitotic drug Telangiectasia bilateral cicatricial ectropion exacerbation of Herpes labialis pain, edema, livedo reticularis erosions (SEDA-7, 166) (SEDA-7, 166) (SEDA-5, 155)... 

Mechlorethamine hydrochloride Nitrogen mustard topical antimitotic drug Carcinogen suppression of immunological defences Stevens-Johnson syndrome (SEDA-22, 172) (19)... 

Vinblastine CT vinca alkaloid, antimitotic drug mdrla, MDRl KO mice [155] TO... 

Figure 20.22) It is reasonable to admit the formation of allylic carbamates also in mitomycines A, B and C which are antimitotic drugs used in cancerology. Presumably the allyl function is created by an elimination reaction involving the departure of an acetalic hydroxy or methoxy group. 

Few of these infections are primary. They have always been liable to occur in patients predisposed to them by serious disease of other kinds, such as cancer, leukemia, uncontrolled diabetes, and alcohol and drug addition. To these predisposing causes have been added in recent years more adventurous surgery, more massive radiotherapy, antimitotic drugs, and corticosteroids. In patients whose normal defenses are impaired or shattered in these various ways, such infections are not surprising, nor is it surprising that their response to treatment is poor. 

Kong, Q. Sun, J. He, R. Liu, E. Sustained-release injections of antimitotic drug. Faming Zhuanli Shenqing Gongkai Shuomingshu CN 1748671, 2006 Chem. Abstr. 2006,145, 110226. 

Shemesh OA, Spira ME (2011) Rescue of neurons from undergoing hallmark tau-induced Alzheimer s disease cell pathologies by the antimitotic drug paclitaxel. Neurobiol Dis 43 163-175. doi 10.1016/j.nbd.2011.03.008... 

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