Molecular spectroscopic and thermodynamic studies on the interaction of anti-platelet drug ticlopidine with calf thymus DNA
| Autor: | Abad Ali, Shumaila Afrin, Mohammed Amir Husain, Shamsuzzaman, Tarique Sarwar, Mohammad Tabish, Yusra Rahman |
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| Rok vydání: | 2017 |
| Předmět: |
Ticlopidine
Thienopyridine Calorimetry 010402 general chemistry 01 natural sciences Analytical Chemistry chemistry.chemical_compound medicine Animals Denaturation (biochemistry) Instrumentation Spectroscopy Quenching (fluorescence) Viscosity 010405 organic chemistry Chemistry Isothermal titration calorimetry DNA Binding constant Atomic and Molecular Physics and Optics 0104 chemical sciences Molecular Docking Simulation Spectrometry Fluorescence Biochemistry Nucleic acid Cattle Spectrophotometry Ultraviolet Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 186:66-75 |
| ISSN: | 1386-1425 |
| DOI: | 10.1016/j.saa.2017.05.073 |
| Popis: | Ticlopidine is an anti-platelet drug which belongs to the thienopyridine structural family and exerts its effect by functioning as an ADP receptor inhibitor. Ticlopidine inhibits the expression of TarO gene in S. aureus and may provide protection against MRSA. Groove binding agents are known to disrupt the transcription factor DNA complex and consequently inhibit gene expression. Understanding the mechanism of interaction of ticlopidine with DNA can prove useful in the development of a rational drug designing system. At present, there is no such study on the interaction of anti-platelet drugs with nucleic acids. A series of biophysical experiments were performed to ascertain the binding mode between ticlopidine and calf thymus DNA. UV-visible and fluorescence spectroscopic experiments confirmed the formation of a complex between ticlopidine and calf thymus DNA. Moreover, the values of binding constant were found to be in the range of 103M-1, which is indicative of groove binding between ticlopidine and calf thymus DNA. These results were further confirmed by studying the effect of denaturation on double stranded DNA, iodide quenching, viscometric studies, thermal melting profile as well as CD spectral analysis. The thermodynamic profile of the interaction was also determined using isothermal titration calorimetric studies. The reaction was found to be endothermic and the parameters obtained were found to be consistent with those of known groove binders. In silico molecular docking studies further corroborated well with the experimental results. |
| Databáze: | OpenAIRE |
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