X-ray crystal structure of a Cu(II) complex with the antiparasitic drug tinidazole, interaction with calf thymus DNA and evidence for antibacterial activity

Abstract

Interaction of metal ions with biologically active molecules like 5-nitroimidazoles modulates their electronic environment and therefore influences their biological function. In the present work, an antiparasitic drug tinidazole (tnz) was selected and a Cu(II) complex of tnz [Cu₂(OAc)₄(tnz)₂] was prepared. A dinuclear paddle-wheel [Cu₂(OAc)₄(tnz)₂] was obtained by single-crystal XRD and further characterized by spectroscopic techniques and cyclic voltammetry. To understand the biological implications of complex formation, interaction of tnz and its complex was studied with calf thymus DNA, bacterial and fungal cell lines. Results of calf thymus DNA interaction using cyclic voltammetry indicate the overall binding constant (K^*) of Cu₂(OAc)₄(tnz)₂ [(59 ± 6) × 10⁴ M⁻¹] is ~17 times greater than that of tnz [(3.3 ± 0.4) × 10⁴ M⁻¹]. Minimum inhibitory concentration values suggest that [Cu₂(OAc)₄(tnz)₂] possesses better antibacterial activity than tnz on both bacterial strains, while the activity on a fungal strain was comparable.

Tinidazole, a 5-nitroimidazole is active on protozoan and bacterial infections. This study made an attempt to see if a Cu(II) complex of tinidazole had comparable efficacy on chosen bacteria and fungi. The prepared complex was characterized by XRD, spectroscopy, elemental analysis cyclic voltammetry. DNA interaction was studied using cyclic voltammetry and fitted by non-linear analysis.

Keywords:

• X-ray diffraction
• Cyclic voltammetry
• Calf thymus DNA
• Binding constant
• MIC

Acknowledgements

Saurabh Das is grateful to the DST-FIST program of the Department of Chemistry, Jadavpur University, for the X-ray diffractometer facility. The authors are grateful to Dr Debojyoti Ghoshal, Department of Chemistry, Jadavpur University, for his help in analyzing the X-ray diffraction data. Saurabh Das is grateful to Prof. Amitava De of Chemical Sciences Division, Saha Institute of Nuclear Physics, Kolkata, for cyclic voltammetry experiments and Prof. Samita Basu (HOD, CSD, SINP) for fluorescence experiments. Saurabh Das is also grateful to Prof. Kalyan K. Mukherjea and his student Shiv Shankar Paul for their help in recording EPR spectra at the departmental facility. Ramesh Chandra Santra expresses his gratitude to the UGC, New Delhi, for a JRF. Piyal Das is grateful to UGC, New Delhi, for a Research Fellowship in the scheme “Scholarship for Meritorious Students”.