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2020 - N-alkylisatin-based microtubule destabilizers bind to the colchicine site on tubulin and retain efficacy in drug resistant acute lymphoblastic leukemia cell lines with less in vitro neurotoxicity

icon pl  Patchliner publication in Cancer Cell International (2020)

Authors: 
Keenan B., Finol-Urdaneta R.K., Hope A., Bremner J.B., Kavallaris M., Lucena-Agell D., Ángela Oliva M., Díaz J.F & Vine K.L.

 Journal: 

Cancer Cell International (2020) doi: 10.1186/s12935-020-01251-6


Abstract: 

Drug resistance and chemotherapy-induced peripheral neuropathy continue to be significant problems in the successful treatment of acute lymphoblastic leukemia (ALL). 5,7-Dibromo-N-alkylisatins, a class of potent microtubule destabilizers, are a promising alternative to traditionally used antimitotics with previous demonstrated efficacy against solid tumours in vivo and ability to overcome P-glycoprotein (P-gp) mediated drug resistance in lymphoma and sarcoma cell lines in vitro. In this study, three di-brominated N-alkylisatins were assessed for their ability to retain potency in vincristine (VCR) and 2-methoxyestradiol (2ME2) resistant ALL cell lines. For the first time, in vitro neurotoxicity was also investigated in order to establish their suitability as candidate drugs for future use in ALL treatment.


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