MDR-reversal activity of chalcones

Antoaneta Ivanova, Daniela Batovska, Helga Engi, Stoyan Parushev, Imre Ocsovszki, Ivanka Kostova, Joseph Molnar

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15 Citations (Scopus)

Abstract

The ability of 11 chalcones with 3,4,5-trimethoxy substitution on ring A to inhibit the transport activity of P-glycoprotein was studied. Flow cytometry was applied in multidrug-resistant human mdr1 gene-transfected mouse lymphoma cells (L 5178 Y). The reversal of multidrug resistance (MDR) was investigated by measuring the accumulation of rhodamine-123 in cancer cells. Verapamil was applied as a positive control. The majority of the tested compounds were proved to be effective inhibitors of the outward transport of rhodamine-123. In the MTT test, chalcones 2, 3, 5 and 7 exhibited the strongest antiproliferative effects, with 50% inhibitory dose (ID50) =0.19, 0.19, 0.29 and 0.14 μg/mL, respectively. The least effective compounds were 1, 4, 8 and 11, with ID50 values in the range of 1.5-3.5 μg/mL. The antiproliferative effect was shown to be affected by the type of substitution at the p-position on ring B. Chalcone 7, with a p-chloro group on ring B, was the most effective in MDR reversal, causing a marked increase in drug accumulation from 0.4 to 40 μg/mL. In combination with epirubicin, compound 7 displayed synergistic properties while compound 3 exhibited an additive effect. The data presented here indicated that some calcone derivatives can be regarded as effective compounds for reversal of MDR.

Original languageEnglish
Pages (from-to)379-384
Number of pages6
JournalIn Vivo
Volume22
Issue number3
Publication statusPublished - May 1 2008

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Keywords

  • Chalcones
  • Efflux pump
  • MDR reversal
  • Multidrug resistance
  • P-glycoprotein

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

Cite this

Ivanova, A., Batovska, D., Engi, H., Parushev, S., Ocsovszki, I., Kostova, I., & Molnar, J. (2008). MDR-reversal activity of chalcones. In Vivo, 22(3), 379-384.