期刊
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
卷 158, 期 -, 页码 274-279出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.jphotobiol.2016.02.032
关键词
Doxorubicin; DNA; tRNA; Intercalation; Groove binding; Conformation; Modeling
资金
- Natural Sciences and Engineering Research Council of Canada (NSERC)
In this review, we have compared the results of multiple spectroscopic studies and molecular modeling of anticancer drug doxorubicin (DOX) bindings to DNA and tRNA. DOX was intercalated into DNA duplex, while tRNA binding is via major and minor grooves. DOX-DNA intercalation is close to A-7, C-5, 'C-19 (H-bonding with DOX NH2 group), G-6, T-8 and T-18 with the free binding energy of -4.99 kcal/mol. DOX-tRNA groove bindings are near A-29, A-31, A-38, C-25, C-27, C-28, *G-30 (H-bonding) and U-41 with the free binding energy of -4.44 kcal/mol. Drug intercalation induced a partial B to A-DNA transition, while tRNA remained in A-family structure. The structural differences observed between DOX bindings to DNA and tRNA can be the main reasons for drug antitumor activity. The results of in vitro MTT assay on SKC01 colon carcinoma are consistent with the observed DNA structural changes. Future research should be focused on finding suitable nanocarriers for delivery of DOX in vivo in order to exploit the full capacity of this very important anticancer drug. (C) 2016 Elsevier B.V. All rights reserved.
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