2. Academic Validation
  3. Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance

Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance

  • Eur J Med Chem. 2016 Jul 19:117:335-54. doi: 10.1016/j.ejmech.2016.03.078.
Veronika F S Pape 1,  Szilárd Tóth 2,  András Füredi 2,  Kornélia Szebényi 2,  Anna Lovrics 2,  Pál Szabó 3,  Michael Wiese 4,  Gergely Szakács 5
Affiliations

Affiliations

  • 1 Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary; Department of Pharmaceutical Chemistry, University of Bonn, Bonn, Germany.
  • 2 Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
  • 3 Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
  • 4 Department of Pharmaceutical Chemistry, University of Bonn, Bonn, Germany. Electronic address: mwiese@uni-bonn.de.
  • 5 Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary. Electronic address: szakacs.gergely@ttk.mta.hu.
PMID: 27161177 DOI: 10.1016/j.ejmech.2016.03.078
Abstract

There is a constant need for new therapies against multidrug resistant (MDR) Cancer. An attractive strategy is to develop chelators that display significant antitumor activity in multidrug resistant Cancer cell lines overexpressing the drug efflux pump P-glycoprotein. In this study we used a panel of sensitive and MDR Cancer cell lines to evaluate the toxicity of picolinylidene and salicylidene thiosemicarbazone, arylhydrazone, as well as picolinylidene and salicylidene hydrazino-benzothiazole derivatives. Our results confirm the collateral sensitivity of MDR cells to isatin-β-thiosemicarbazones, and identify several chelator scaffolds with a potential to overcome multidrug resistance. Analysis of structure-activity-relationships within the investigated compound library indicates that NNS and NNN donor chelators show superior toxicity as compared to ONS derivatives regardless of the resistance status of the cells.

Keywords

Antitumor agents; Cancer; Chelators; Multidrug resistance; Schiff bases.

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