Journal of Enzyme Inhibition and Medicinal Chemistry (Jan 2020)

Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity

  • Mikhail Krasavin,
  • Tatiana Sharonova,
  • Vladimir Sharoyko,
  • Daniil Zhukovsky,
  • Stanislav Kalinin,
  • Raivis Žalubovskis,
  • Tatiana Tennikova,
  • Claudiu T. Supuran

DOI
https://doi.org/10.1080/14756366.2020.1734800
Journal volume & issue
Vol. 35, no. 1
pp. 665 – 671

Abstract

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A hypothesis that simultaneous targeting cancer-related carbonic anhydrase hCA IX and hCA XII isoforms (whose overexpression is a cancer cell’s defence mechanism against hypoxia) along with thioredoxin reductase (overexpressed in cancers as a defence against oxidative stress) may lead to synergistic antiproliferative effects was confirmed by testing combinations of the two inhibitor classes against pancreatic cancer cells (PANC-1). Combining both pharmacophoric motifs within one molecule led to a sharp increase of cytotoxicity. This preliminary observation sets the ground for a fundamentally new approach to anticancer agent design.

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