Antitubulin activity

The thiocarbonyl group is a classic bioisosteric replacement for the carbonyl group which has been widely exploited in medicinal chemistry. This is illustrated with the preparation of thioketones derived from thiocolchicine283 and isothiocolchicine284 which exhibited high antitubulin activity (equation 38). 

Antitubulin Activity and Acute Toxicity of Phenolic Colchicinoids and Thio Congeners"... 

Finally, one has to mention the work of Levy and co-workers who described the semi-synthesis of D-ring seco-rhazinilam analogues from (-)-tabersonine using an Emde degradation and /nCPBA oxidation [90]. The. veco-analogue 50 is only twice less active than rhazinilam on the inhibition of microtubules disassembly, illustrating that the absence of the D-ring is not strictly deleterious to the antitubulin activity [91,92]. 

Table 1. Antitubulin activity and cytotoxicity of selected steganes [42,43,149]...

The antiproliferative and antitubulin activities of libraries of pyranopyridones and pyranoquinolones 147 (Scheme 28) derived from aldehydes, malononitrile and pyridones 146 have been examined [65]. The compounds were evaluated for their ability to reduce cell viability by 50% after 48 h of treatment relative to control. The HeLa and MCE-7 cell fines were used as models for human cervical and breast adenocarcinoma, respectively. Numerous compounds exhibited submicromolar antiproliferative activities with the quinolones being more potent than their pyridine counterparts (Eig. 20). Because of the structural similarity of pyranopyridones with chromene scaffolds known to inhibit tubulin polymerization, compounds 149 and 150 were further evaluated in Jurkat cells for their apoptotic... 

Magedov IV, Manpadi M, Ogasawara MA (2008) Stmctural simplification of bioactive natural products with multicomponent synthesis. 2. Antiproliferative and antitubulin activities of pyrano[3, 2-c]pyridones and pyrano[3, 2-c]quionolones. J Med Chem 51 2561-2570... 

Shi Q, Chen K, Brossi A, Verdier-Pinard P, Hamel E, McPhail AT, Lee KH. Antitumor agents 184. Syntheses and antitubulin activity of compounds derived from reaction of thiocolchicone with amines lactams, alcohols, and esters analogs of allothio-colchicinoids. Helv. Chim. Acta 1998 81 1023-1037. 

When the former protocol was applied to Combretastatin A-1, attempted conversion of the mesylate to azide failed and took an other course, affording a tetraidro-benzofuran derivative, most likely arising from nucleophilic attack of a deprotected 2 hydroxyl on the mesylate [17]. Preliminary biological tests, still in course, showed a potential antitubulin activity of the benzotetraidrofuran derivative. 

F Zavala, D Guenard, JP Robin, E Brown. Structure-antitubulin activity relationships in steganacin congeners and analogues. Inhibition of tubulin polymerization in vitro by (+)-isodeoxypodophyllotoxin. J Med Chem 23 546-549, 1980. 

A microtubule inhibitor, rhizoxin (Fig. 1) was found in the culture filtrate of Rhizopus chinensis (j>). Subsequently, Iwasaki et al. (7 ) determined the chemical structure of this compound, and the antitubulin activity of rhizoxin was characterized using porcine brain tubulin (j3). 

Takahashi, M., Iwasaki, S., Kobayashi, H., Okuda, S., Murai, T., Sato, Y., Haraguchi-Hiraoka, T., and Nagano, H. (1987). Studies on macrocyclic lactone antibiotics. XI. Antimitotic and antitubulin activity of new antitumor antibiotics, rhizoxin and its homologs. J. Antibiot. 40, 66-72. 

Bhattacharya G, Herman J, Delffn D et al. Synthesis and antitubulin activity of NU and N -substituted 3,5-dinitro sulfanilamides against African Trypanosomes and Leishmania. J Med Chem 2004 47 1823-1832. 

Ikeyama S, Thkeuchi M 1981 Antitubulin activities of ansamitocins and maytansinoids. Biochem Pharmacol 30 2421-2425... 

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