Combining Carbonic Anhydrase and Thioredoxin Reductase Inhibitory Motifs within a Single Molecule Dramatically Increases Its Cytotoxicity

Journal of Enzyme Inhibition and Medicinal Chemistry 2020
Mikhail Krasavin, Tatiana Sharonova, Vladimir Sharoyko, Daniil Zhukovsky, Stanislav Kalinin, Raivis Žalubovskis, Tatiana Tennikova, Claudiu T. Supuran

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.

Atslēgas vārdi
Anticancer agents, cancer cell defence mechanisms, carbonic anhydrase inhibition, dual pharmacophores, hypoxia, Michael acceptors, oxidative stress, synergistic effect, thioredoxin reductase inhibition, zinc-binding group
DOI
10.1080/14756366.2020.1734800
Hipersaite
https://www.tandfonline.com/doi/full/10.1080/14756366.2020.1734800

Krasavin, M., Sharonova, T., Sharoyko, V., Zhukovsky, D., Kalinin, S., Žalubovskis, R., Tennikova, T., Supuran, C. Combining Carbonic Anhydrase and Thioredoxin Reductase Inhibitory Motifs within a Single Molecule Dramatically Increases Its Cytotoxicity. Journal of Enzyme Inhibition and Medicinal Chemistry, 2020, Vol. 35, No. 1, 665.-671.lpp. ISSN 1475-6366. e-ISSN 1475-6374. Pieejams: doi:10.1080/14756366.2020.1734800

Publikācijas valoda
English (en)