RNA targeting by an anthracycline drug: spectroscopic and in silico 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 × 103 M-1) 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.

Structural investigation of idarubicin-DNA interaction: spectroscopic and molecular docking study.

Mechanistic understanding of interaction of drugs with their target molecule is important for development of new drug therapy regimes. Idarubicin (IDR) is a potent chemotherapeutic agent used to treat variety of cancers. Structural and conformational studies associated with binding of IDR on DNA double helix were investigated through spectroscopic techniques and molecular docking studies. Interaction studies were done by preparing different molar ratios of IDR with constant DNA concentration under physiological conditions. FTIR spectroscopy, UV-vis spectroscopy, CD spectroscopy were used to analyze interaction between IDR and DNA. FTIR results suggest IDR binds at major groove of DNA duplex via guanine and cytosine bases. UV-vis spectroscopy result indicates IDR gets intercalated between the DNA bases. The calculated binding constant shows that IDR is a moderate binder. Slight perturbation in the native B-conformation of DNA was observed in all IDR-DNA molar ratios examined. In silico investigation of IDR binding with DNA is in agreement with our experimental results, providing structural insight into DNA binding properties of IDR.

Spectroscopic and molecular docking studies on chlorambucil interaction with DNA.

Chlorambucil (CMB) is an anticancer drug used for the treatment of variety of cancers. Structural and conformational changes associated with DNA after binding with CMB were explored using spectroscopic techniques to get insight into the mechanism of action of CMB at molecular level. Different molar ratios of CMB-DNA complex were prepared with constant DNA concentration under physiological conditions. FTIR spectroscopy, UV-visible spectroscopy, CD spectroscopy and molecular docking studies were employed to determine the binding site and binding constant of CMB with DNA. The results show CMB binds DNA through nitrogenous bases (thymine, guanine and cytosine). The binding constant was calculated to be 1.3 × 10³ M⁻¹, which suggests weak binding of CMB with DNA double helix. FTIR and CD results show that CMB do not disturb native B-conformation of DNA and it continues to remain in its B conformation even at higher concentrations of CMB. The molecular docking results are in corroboration with our experimental results and provides structural insight into the interaction site.

Binding of an indole alkaloid, vinblastine to double stranded DNA: a spectroscopic insight in to nature and strength of interaction.

Vinblastine is a chemotherapeutic drug, used for the treatment of various cancers. It functions by interfering with DNA in fast growing cells and preventing them from reproducing. The present work is focused on the interaction of vinblastine with double stranded DNA in aqueous solution. Fourier transform infrared and UV-Visible absorption spectroscopy were used to analyze the interaction of vinblastine with calf-thymus DNA. FTIR analysis showed binding of vinblastine through A-T and G-C base pairs of DNA along with its phosphate backbone. UV-Vis spectroscopy results suggested the intercalation of drug in between the base pairs of DNA double helix. The binding constant estimated for vinblastine-DNA association was found to be K=1.7×10(3)M(-1). Molecular docking was performed and the results showed adenine base binding of vinblastine with DNA. Furthermore spectroscopic results revealed that formation of vinblastine-DNA complex resulted in no major change in the B-conformation of DNA.

FTIR and circular dichroism spectroscopic study of interaction of 5-fluorouracil with DNA.

5-Fluorouracil (5FU) is an anticancer chemotherapeutic drug which exerts cytotoxic effect by inhibiting cellular DNA replication. In the present study, we explore the binding of 5FU with DNA and resulting structural and conformational changes on DNA duplex. UV-visible, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopic techniques were employed to explore these interactions. A constant concentration of calf thymus DNA was incubated with varying concentrations of 5FU. UV-visible and FTIR spectroscopic results revealed that intercalation is the primary mode of interaction between 5FU and nitrogenous bases of the nucleic acid. The binding constant was found to be 9.7×10(4); which is indicative of moderate type of interaction between 5FU and DNA duplex. It was also observed that 5FU intercalates slightly more between AT base pairs compared to GC pairs. FTIR and circular dichroism spectroscopic results revealed that 5FU disturbs native B-conformation of DNA though, DNA remains in its B conformation even at higher concentrations of 5FU.