期刊
BIOORGANIC CHEMISTRY
卷 76, 期 -, 页码 392-399出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2017.12.005
关键词
Natural products; Fluorescent assay; Tdp1, molecular modelling; Chemical space; Amine; Cytotoxicity; Adamantanes
资金
- Russian Scientific Foundation [16-13-10074]
The ability of a number of nitrogen-containing compounds that simultaneously carry the adamantane and monoterpene moieties to inhibit Tdp1, an important enzyme of the DNA repair system, is studied. Inhibition of this enzyme has the potential to overcome chemotherapeutic resistance of some tumor types. Compound (+)-3c synthesized from 1-aminoadamantane and (+)-myrtenal, and compound 4a produced from 2-aminoadamantane and citronellal were found to be most potent as they inhibited Tdp1 with IC50 values of 6 and 3.5 mu M, respectively. These compounds proved to have low cytotoxicity in colon HCT-116 and lung A-549 human tumor cell lines (CC50 > 50 mu M). It was demonstrated that compound 4a at 10 mu M enhanced cytotoxicity of topotecan, a topoisomerase 1 poison in clinical use, against HCT-116 more than fivefold and to a lesser extent of 1.5 increase in potency for A-549. (C) 2017 Elsevier Inc. All rights reserved.
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