Synthesis, crystal structure and DNA binding interactions of ethyl 2-(2-acetamidothiazol-4-yl) acetate: Theoretical and experimental investigations

作者：Iqbal, Zafar; Ashraf, Zaman^*; Abas, Mujahid; Tahir, Muhammad Nawaz; Jabeen, Erum; Paracha, Rehan Zafar; Nisar, Maryum; Ahmad, Safeer

来源：Journal of Molecular Structure, 2019, 1198: UNSP 126903.

DOI：10.1016/j.molstruc.2019.126903

• DNA binding
• Thiazole
• Single crystal X-ray
• DFT calculations
• Molecular docking

The present study describes the efficient synthesis, structural characterization and DNA binding interactions of ethyl 2-(2-acetamidothiazol-4-yl)acetate 2. Theoretically and experimentally determined bond lengths, angles and DNA binding interactions are compared. The chemical structure of the synthesized compound 2 was confirmed by spectral data and single crystal X-ray diffraction. The presence of -NH signal at 12.16 ppm in (HNMR)-H-1 spectrum and carbonyl carbon at 170.5 ppm in (CNMR)-C-13 spectrum confirmed the formation of ethyl 2-(2-acetamidothiazol-4-yl)acetate 2. The bond lengths and angles calculated theoretically are in good agreement with experimentally determined values. Molecular docking studies of synthesized compound 2 against five different DNA structures were performed to check its binding affinity with these targets. It was found that compound 2 binds well with DNA (PDB 1BPX) having binding energy value -5.7 kcal/mol. The DNA binding interactions was also determined experimentally by spectrophotometric and electrochemical methods. The results showed that compound 2 binds with DNA through intercalation and groove binding which reflected the mixed binding mode. The binding constants (K-b) calculated from these results are 1.45 x 10(3)M(-1) (UV-Vis spectroscopy), 1.41 x 10(3)M(-1) (Fluorescence spectroscopy) and 1.39 x 10(3)M(-1) (Cyclic voltammetry) also revealed strong binding. Based upon our results it was proposed that the synthesized compound 2 may act as a lead structure to design more potent antitumor agents.