Title: Synthesis and multidrug resistance reversal activity of 1,2-disubstituted tetrahydroisoquinoline derivatives
Authors: Mihályi, Attila
Gáspár, Róbert
Zalán, Zita
Lázár, László
Fülöp, Ferenc
de Witte, Peter # ×
Issue Date: Jan-2004
Series Title: Anticancer research vol:24 issue:3a pages:1631-6
Abstract: 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''-(alpha-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.
ISSN: 0250-7005
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Pharmaceutical Biology (-)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science