Antimitotic agent

The remarkable success of taxol in treatment of breast and ovarian cancers stimulated research efforts to synthesize taxol directly and to identify new antimitotic agents that, like taxol, stimulate microtubule polymerization. 

Synthetic study of 4-thiazoline derivative curacin A, a novel antimitotic agent isolated from cyanobacterium Lyngbya majuscula 99YGK552. 

Podophyllotoxin, a plant lignan, is a potent antimitotic agent (Figure 6.61). An enantioselective synthesis of (—)-podophyllotoxin was achieved via the enzymatic desymmetrization of an advanced meso-diacetate, through PPL-mediated diester hydrolysis [157]. 

The compound curacin A 207 is a novel antimitotic agent isolated from the Caribbean cyanobacterium Lyngbya majuscula. The compound consists of a disubstituted thiazoline bearing a chiral cyclopropane ring and an aliphatic side chain. Scheme 5-67 depicts the construction of the cyclopropane ring using an asymmetric cyclopropanation reaction.122... 

Antimitotic agents Vinca alkaloids Lung adenocarcinoma... 

Manfredi JJ, Horwitz SB. T axol an antimitotic agent with anew mechanism of action. Pharmacol Ther 1984 25(1) 83—125. 

Rao VC, Mehendale HM. 1993. Effect of antimitotic agent colchine on carbon tetrachloride toxicity. Arch Toxicol 67 392-400. 

L.G. Davidse and W. Flach, Differential Binding of Benzimidazol-2-yl Carbamate to Fungal Tubulin as a Mechanism of Resistance to this Antimitotic Agent in Mutant Strains of Aspergillus nidulans J. Cell. Biol., 1977, 72, 174-193. 

Reaction of an -substituted pyrrole with an alkynic dienophile provides access to a 3,4-disubstituted pyrrole through a Diels-Alder/retro-Diels-Alder cycloaddition process (73CJC1089). The 3,4-pyrroledicarboxylic ester (206) prepared in this way has been converted to the antimitotic agent Verrucarin E (207 Scheme 44). 

It was found that 1 acted as an antimitotic agent, not binding to tubulin, but by disorganizing the microtubule network in some fashion. In addition, it is a DNA minor groove guanine-specific alkylating agent [1]. The Et s showed potent inhibition of DNA and RNA synthesis and of RNA polymerase activity, but its inhibition of DNA polymerase activity is much less marked [75]. The potent activity of Et s was attributed, at least in part, to the unit C since the related saframycin A lacks this unit and has lower efficacy than Et 729 in comparable tumor models [74, 75]. More recent structural information on Et 743-DNA adduct was obtained by NMR spectroscopy [78]. An enantioselective total synthesis of Et 743 has been achieved by Corey et al. [79]. 

Anderson and co-workers86 used the cycloaddition of acetylenic esters to 19a and 19 (R = COPh) in the synthesis of the antimitotic agent Verrucarin E (28). The pyrrole 19a and DMAD gave 35% of 21a, whereas 19 (R = COPh) gave 67% of 21 (R = COPh) and 23% of recovered starting material 1-benzoylpyrrole gave 54% of 29 with DEAD. Further transformations produced the natural product. 

Li T, Shih C (2002) Structure Activity Relationships of Cryptophycins, A Novel Class of Antitumor Antimitotic Agents. Front Biotechnol Pharmaceut 3 1972... 

Colchicine is an antimitotic agent and is widely employed as an experimental tool in the study of cell division and function. 

The structurally novel antimitotic agent curacin A (1) was prepared with an overall yield of 2.5 % for the longest linear synthesis. Three of the four stereogenic centers were built up using asymmetric transformations one was derived from a chiral pool substrate. Key steps of the total synthesis are a hydrozirconation - transmetalation protocol, the stereoselective formation of the acyclic triene segment via enol triflate chemistry and another hydrozirconation followed by an isocyanide insertion. For the preparation of the heterocyclic moiety of curacin A (1) the oxazoline - thiazoline conversion provides efficient access to the sensitive marine natural product. 

The above-described problem demonstrates the first enantioselective synthesis of dysidiolide, a C25 isoprenoid antimitotic agent. The central transformations are the sulfenylation-dehydrosulfenylation sequence to prepare an a,/5-tnone, the biomimetic cationic 1,2-rearrangement to form stereoselectively the bicyclic scaffold, vinyl cuprate displacement of an iodide furnishing the C-l side chain and the photochemical oxidation of furan to generate the j hydroxy-butenolide functionality. 

Bai, R.L., G.R. Pettit, and E. Hamel. 1990. Binding of dolastatin 10 to tubulin at a distinct site for peptide antimitotic agents near the exchangeable nucleotide and Vinca alkaloid sites./. Biol. Chem. 

Muller, W. E. G., Diehl-Seifert, B., Sobel, C., Bechtold, A., Kljajic, Z., and Dorn, A., Sponge secondary metabolites biochemical and ultrastructural localization of the antimitotic agent avarol in Dysidea avara, J. Histochem. Cytochem., 34, 1687, 1986. 

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. 

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