Further exploration of DVD-445 as a lead thioredoxin reductase (TrxR) inhibitor for cancer therapy: Optimization of potency and evaluation of anticancer potential

Mirna Jovanović, Daniil Zhukovsky, Ana Podolski-Renić, Raivis Žalubovskis, Dmitry Dar'in, Vladimir Sharoyko, Tatiana Tennikova, Milica Pešić, Mikhail Krasavin

Research output

1 Citation (Scopus)

Abstract

A series of analogs of the earlier reported lead compound DVD-445 (thioredoxin reductase inhibitor with anticancer activity) has been synthesized via a modified Ugi reaction and investigated. Seven most potent compounds (with IC50 below 5.00 μM against recombinant rTrxR1 enzyme) were examined for their effect on cell growth and viability, oxidative stress induction and P-glycoprotein (P-gp) inhibition in human glioblastoma cells cell line U87 and its corresponding multidrug resistant (MDR) cell line U87-TxR. Several of these frontrunner compounds were shown to be superior over DVD-445. Besides providing promising candidates for anticancer therapy, our study further validates the small electrophilic Ugi Michael acceptor (UMA) chemotype as efficacious inhibitor of thioredoxin reductase.

Original languageEnglish
Article number112119
JournalEuropean Journal of Medicinal Chemistry
Volume191
Early online date6 Feb 2020
DOIs
Publication statusPublished - 1 Apr 2020

Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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