Jump to main content
Jump to site search


Synthesizing a CuII complex of tinidazole to tune the generation of the nitro radical anion in order to strike a balance between efficacy and toxic side effects

Author affiliations

Abstract

A monomeric complex of Cu(II) with tinidazole [Cu(tnz)2Cl2] was synthesized. The complex decreases the formation of the nitro-radical anion (NO2˙), which was followed by an enzyme assay involving xanthine oxidase, a model nitro-reductase. It has a binding constant value with DNA comparable to that of tinidazole. In addition to the drug efficacy of the nitro radical anion, it also has neurotoxic side effects; so it is essential to control its formation to an optimum, sufficient for bringing about cytotoxic activity on disease causing microbes but avoiding excess that could make it neurotoxic. If this is achieved through modification of the 5-nitroimidazole moiety then too much NO2˙ would not be generated, implying that the chances of the drug causing any harm to the host due to toxic side effects could be reduced. However, with decreased NO2˙ formation, in an effort to decrease complications, a certain amount of therapeutic efficacy would be compromised. Therefore, the biological activity of tinidazole and its modified form, a monomeric complex, was investigated to see how the latter compares with tinidazole under comparable conditions. Studies revealed that, in spite of decreased NO2˙ formation, the complex showed similar activity to that of tinidazole on two bacterial strains and an amoeba strain, implying that it has other attributes, not known for 5-nitroimidazoles, that enable it to match the efficacy of tinidazole. The study suggests that there is a substantial decrease in NO2˙ due to the formation of the tinidazole complex, meaning that the toxic side effects are likely to be reduced which is an advantage as it would improve the therapeutic index.

Graphical abstract: Synthesizing a CuII complex of tinidazole to tune the generation of the nitro radical anion in order to strike a balance between efficacy and toxic side effects

Back to tab navigation
Please wait while Download options loads

Supplementary files

Publication details

The article was received on 21 Jan 2017, accepted on 24 Apr 2017 and first published on 25 Apr 2017


Article type: Paper
DOI: 10.1039/C7NJ00261K
Citation: New J. Chem., 2017, Advance Article
  •   Request permissions

    Synthesizing a CuII complex of tinidazole to tune the generation of the nitro radical anion in order to strike a balance between efficacy and toxic side effects

    R. C. Santra, D. Ganguly, S. Jana, N. Banyal, J. Singh, A. Saha, S. Chattopadhyay, K. Mukhopadhyay and S. Das, New J. Chem., 2017, Advance Article , DOI: 10.1039/C7NJ00261K

Search articles by author