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

Journal of Enzyme Inhibition and Medicinal Chemistry
Mikhail KrasavinClaudiu T Supuran

Abstract

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.

References

Nov 10, 2006·Seminars in Cancer Biology·Elias S J Arnér, Arne Holmgren
Oct 7, 2008·Oncogene·T J Stewart, S I Abrams
May 31, 2014·Current Protein & Peptide Science·Fulvio SaccocciaAndrea Bellelli
Nov 3, 2016·Anti-cancer Agents in Medicinal Chemistry·Laurent SchwartzKhalid O Alfarouk
Dec 16, 2016·Expert Opinion on Therapeutic Patents·Baoxin ZhangJianguo Fang
Jun 27, 2017·Trends in Pharmacological Sciences·Junmin ZhangJianguo Fang
Sep 21, 2017·Metabolites·Claudiu T Supuran
Feb 13, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Olga BakulinaMikhail Krasavin
Apr 10, 2019·Journal of Medicinal Chemistry·Mianli BianWukun Liu

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Citations

Dec 29, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Anna Jastrząb, Elżbieta Skrzydlewska
Mar 6, 2021·Expert Opinion on Therapeutic Patents·Evgeny Chupakhin, Mikhail Krasavin
Apr 27, 2021·Colloids and Surfaces. B, Biointerfaces·Sizhu RenYanlin Yuan
Jul 31, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran

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Methods Mentioned

BETA
column chromatography

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