Synthesis and multidrug resistance reversal activity of 1,2-disubstituted tetrahydroisoquinoline derivatives

Attila Mihályi, Róbert Gáspár, Zita Zalán, László Lázár, Ferenc Fülöp, Peter A.M. De Witte

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11 Citations (Scopus)


Background: Cancer treatment often fails due to multidrug resistance (MDR) of the tumor cells. One of the major causes is overexpression of P-glycoprotein (P-gp). Materials and Methods: By N-substitution reactions of diamine, amino acid and amino alcohol derivatives with 1-substituted tetrahydroisoquinoline skeleton, structurally diverse 1,2-disubstituted 1,2,3,4-tetrahydroisoquinolines were synthesized. The compounds were assayed as P-gp inhibitors using a standard functional assay with rhodamine (6G) on MCF-7/Adr cells. Cytotoxicity was investigated on HeLa cells using an antiproliferative assay. Results: Five of the 24 compounds showed greater P-gp inhibition than the control compound verapamil with AC50 values (concentration of the compound eliciting 50% of the maximal rhodamine 6G accumulation) significantly lower than that of verapamil. Conclusion: Novel compounds were synthesized that showed MDR-reversal effect. One of them, (1′R*2R*)-2-{2′-[2″-hydroxy- 3‴(a-naphthyloxy)propyl]-6′,7′-dimethoxy-1′,2′,3, ′4′-tetrahydro-1′-isoquinolyl}propan-1-ol hydrochloride, showed two times higher efficacy than verapamil at 10 times lower concentrations. The outcome makes this molecule an attractive subject for further investigation and development.

Original languageEnglish
Pages (from-to)1631-1636
Number of pages6
JournalAnticancer research
Issue number3 A
Publication statusPublished - May 1 2004



  • Multidrug resistance
  • P-glycoprotein
  • Tetrahydroisoquinolines

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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