Microtubule targeting agents

Keywords Microtubule targeting agents, Molecular docking, Molecular modeling, Pharmacophore, Quantitative structure-activity relationships, Tubulin... 

Fojo AT, Menefee M. Microtubule targeting agents basic mechanisms of multidrug resistance (MDR). Semin Oncol 2005 32 S3-S8. 

Romagnoli et al. have reported a convergent synthesis of a class of microtubule targeting agents where they aj lied the Suzuki-Miyaura reaction to highly substituted 5-bromothiazoles. With various aryl boronic acid, highly substituted thiazole derivatives were prepared and evaluated for their anti-proliferative activity against a panel of human tumor cell lines. 

Microtubule-targeting agents are amply used in chemotherapy and recent evidence suggests that they require of mitochondria for their anti-cancer effectiveness (Figure 6). Microtubule-destabilizing drugs such as alkaloids colchicine (used for gout treatment and familial mediterranean fever [162]) and nocodazole produce increase of free tubulin and in parallel decrease of Av /m in human hepatoma cells [163], In contrast, decrease of free tubulin... 

A. Rovini, A. Savry, D. Braguer, and M. Carre, Microtubule-targeted agents when mitochondria become essential to chemotherapy. Biochim. Biophys. Acta., 1807 (2011) 679-88. 

Some microtubule targeting agents like colchicine (41), as well as certain anticancer agents... 

Heam BR, Shaw SJ, Myles DC (2006) Microtubule targeting agents. Comp Med Chem II 7 81-110... 

Paclitaxel is a well-established antiproliferative agent with a microtubule-targeting pharmacologic activity (37,42,43). As an anticancer agent, paclitaxel causes polymerization and stabilization of microtubules (43-45). The stabilization of microtubule dynamics by paclitaxel can interrupt many cellular processes, including cell division, migration, activation, maintenance of cytoskeletal framework, and intracellular as well as transmembrane protein transport (42,46,47). 

Bhalla, K.N. (2003). Microtubule-targeted anticancer agents and apeptosis. Oncogene, Vol.22, No.57, (December 2003), pp. 9075-9086, ISSN 0950-9232... 

Gibson S, Widmann C, Johnson GL. Differential involvement of MEK kinase 1 (MEKKl) in the induction of apoptosis in response to microtubule-targeted drugs versus DNA damaging agents. J Biol Chem 1999 274(16) 10916-10922. 

Other anticancer agents have distinct mechanisms paclitaxel and its relatives target microtubules as do the vinca alkaloids. Antiestrogens and antiandrogens target estrogen and androgen receptors. 

Zhou J, Giannakakou P. Targeting microtubules for cancer chemotherapy. Curr Med Chem Anticancer Agents. 2005 5 65-71. 

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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