Review on the binding of anticancer drug doxorubicin with DNA and tRNA: Structural models and antitumor activity
D. Agudelo, P. Bourassa, G. Bérubé, H.A. Tajmir-Riahi
Journal of Photochemistry and Photobiology B: Biology
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 NH2group), 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.
Circular dichroism, Secondary structure, Ligand binding, Biochemistry