312299-31-3Relevant academic research and scientific papers
Microtubule destabilizing sulfonamides as an alternative to taxane-based chemotherapy
González, Myriam,Ovejero-Sánchez, María,Vicente-Blázquez, Alba,álvarez, Raquel,Herrero, Ana B.,Medarde, Manuel,González-Sarmiento, Rogelio,Peláez, Rafael
, p. 1 - 21 (2021/02/19)
Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most com-monly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes —first-l
N-(1'-naphthyl)-3,4,5-trimethoxybenzohydrazide as microtubule destabilizer: Synthesis, cytotoxicity, inhibition of cell migration and in vivo activity against acute lymphoblastic leukemia
Salum, Lívia B.,Mascarello, Alessandra,Canevarolo, Rafael R.,Altei, Wanessa F.,Laranjeira, Angelo B.A.,Neuenfeldt, Patrícia D.,Stumpf, Taisa R.,Chiaradia-Delatorre, Louise D.,Vollmer, Laura L.,Daghestani, Hikmat N.,De Souza Melo, Carolina P.,Silveira, André B.,Leal, Paulo C.,Frederico, Marisa J.S.,Do Nascimento, Leandro F.,Santos, Adair R.S.,Andricopulo, Adriano D.,Day, Billy W.,Yunes, Rosendo A.,Vogt, Andreas,Yunes, José A.,Nunes, Ricardo J.
, p. 504 - 518 (2015/05/13)
Tubulin-interacting agents, like vinca alkaloid and taxanes, play a fundamental role in cancer chemotherapy, making cellular microtubules (MT), one of the few validated anticancer targets. Cancer resistance to classical MT inhibitors has motivated the development of novel molecules with increased efficacy and lower toxicity. Aiming at designing structurally-simple inhibitors of MT assembly, we synthesized a series of thirty-one 3,4,5-trimethoxy-hydrazones and twenty-five derivatives or analogs. Docking simulations suggested that a representative N-acylhydrazone could adopt an appropriate stereochemistry inside the colchicine-binding domain of tubulin. Several of these compounds showed anti-leukemia effects in the nanomolar concentration range. Interference with MT polymerization was validated by the compounds' ability to inhibit MT assembly at the biochemical and cellular level. Selective toxicity investigations done with the most potent compound, a 3,4,5-trimethoxy-hydrazone with a 1-naphthyl group, showed remarkably selective toxicity against leukemia cells in comparison with stimulated normal lymphocytes, and no acute toxicity in vivo. Finally, this molecule was as active as vincristine in a murine model of human acute lymphoblastic leukemia at a weekly dose of 1 mg/kg.
Cell proliferation inhibitors
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, (2008/06/13)
Compounds having formula (I) inhibit cellular proliferation. Processes for the preparation of the compounds, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds are disclosed.
