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Robustadial A and B from Eucalyptus globulus Labill. and their anticancer activity as selective tyrosyl‐DNA phosphodiesterase 2 inhibitors
Author(s) -
Zhang Yu,
He XiaoZhi,
Yang Hao,
Liu HaiYang,
An LinKun
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.7207
Subject(s) - du145 , topoisomerase , cell culture , etoposide , cancer cell , chemistry , cancer , cancer research , biology , biochemistry , microbiology and biotechnology , dna , genetics , lncap , chemotherapy
Tyrosyl‐DNA phosphodiesterase 2 (TDP2) is a recently discovered DNA repair enzyme that can repair topoisomerase 2‐mediated DNA damage, resulting in cancer cell resistance. In this study, two compounds, robustadial A and B, were isolated from a fraction of the ethyl acetate extract of Eucalyptus globulus Labill. fruits based on TDP2 inhibition screening. The biological experiments indicated that robustadial A and B have TDP2 inhibitory activity with EC 50 values of 17 and 42 μM, respectively, but no tyrosyl‐DNA phosphodiesterase 1 inhibition at 100 μM. Robustadial A showed significant synergistic effects with the anticancer drug etoposide in four human cancer cell lines, non‐small cell lung cancer cell line (A549), prostate cancer cell line (DU145), breast cancer cell line (MCF‐7), colorectal adenocarcinoma cell line (HCT‐116), and chicken lymphoma cell line (DT40), and chicken lymphoma cell line complementation with human TDP2 (DT40 hTDP2) with combination index values ranging from 0.21 to 0.74. This work will facilitate future efforts for the development of robustadial A‐based TDP2 selective inhibitors.