RNA targeting by an anthracycline drug: spectroscopic and evaluation of epirubicin interaction with tRNA.

Anthracyclines are putative anticancer agents used to treat a wide range of cancers. Among these anthracyclines, epirubicin is derived from the doxorubicin by the subtle difference in the orientation of C4-hydroxyl group at sugar molecule. Epirubicin has great significance as it has propitious anticancer potential with lesser cardiotoxicity and faster elimination from the body. The present study is done to understand the molecular aspect of epirubicin binding to tRNA. We have used various spectroscopic techniques like Fourier transform infrared spectroscopy (FTIR), absorption spectroscopy and circular dichroism to illustrate the binding sites, the extent of binding and conformational changes associated with tRNA after interacting with epirubicin. From infrared studies, we infer that epirubicin interacts with guanine and uracil bases of tRNA. Results obtained from infrared and CD studies suggest that epirubicin complexation with tRNA does not result in any conformational change in tRNA structure. Binding constant (2.1 × 10 M) calculated from the absorbance data illustrates that epirubicin has a weak interaction with tRNA molecule. These spectroscopic results like the binding site of epirubicin and binding energy of epirubicin-tRNA complex were also verified by the molecular docking. Results of the present study provide information that aids in the development of efficient RNA targeted drugs from the existing drugs by certain chemical modification in their structure resulting in lesser side effects and better efficacy.Communicated by Ramaswamy H. Sarma.