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Racemic total synthesis and evaluation of the biological activities of the isoquinoline–benzylisoquinoline alkaloid muraricine
Author(s) -
Schütz Ramona,
Müller Martin,
Gerndt Susanne,
Bartel Karin,
Bracher Franz
Publication year - 2020
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.202000106
Subject(s) - benzylisoquinoline , alkaloid , isoquinoline , chemistry , vincristine , stereochemistry , multiple drug resistance , tetrahydroisoquinoline , pharmacology , biochemistry , chemotherapy , biology , enzyme , biosynthesis , cyclophosphamide , antibiotics , genetics
The first racemic total synthesis of the isoquinoline–benzylisoquinoline alkaloid muraricine is reported herein. Pharmacological characterization identified muraricine as a moderate inhibitor of P‐glycoprotein, a crucial factor of multidrug resistance in cancer. When combined with vincristine, muraricine partly reversed the chemoresistance of vincristine‐resistant leukemia cells at a nontoxic concentration. Furthermore, no cytotoxic effects on noncancerous human cells in therapeutically relevant concentrations were observed.