In Situ Reactivity of Electrochemically Generated Nitro Radical Anion on Tinidazole and Its Monomeric and Dimeric Cu(II) Complexes on Model Biological Targets with Relative Manifestation of Preventing Bacterial Biofilm Formation

[Image: see text] Formation of nitro radical anion (−NO(2)(•–)) and other reduction products of 5-nitroimidazoles, although important for antimicrobial activity, makes the drugs neurotoxic. Hence, an appropriate generation and their role in the free radical pathway needs proper realization. This was attempted by studying the action of tinidazole and its Cu(II) complexes on model targets (nucleic acid bases and calf thymus DNA). Results obtained were correlated with studies on biological species where prevention of biofilm formation on Staphylococcus aureus and Pseudomonas aeruginosa was followed. Tinidazole and its Cu(II) complexes subjected to electrochemical reduction in aqueous solution, under de-aerated conditions, interact with model nucleic acid bases and calf thymus DNA. These model targets were followed to realize what happens when such compounds undergo enzymatic reduction within cells of microorganisms that they eventually kill. Studies reveal that Cu(II) complexes were better in modifying nucleic acid bases and calf thymus DNA than tinidazole; damage caused to nucleic acid bases was correlated with that caused to DNA, indicating that compounds affect DNA rich in thymine and adenine. Minimum bactericidal concentrations on sessile S. aureus and P. aeruginosa for the monomeric Cu(II) complex were 12.5 and 20.25 μM respectively, while those for the dimeric complex were 40.0 and 45.0 μM, respectively. Biofilm formation by P. aeruginosa and S. aureus and viability count of sessile cells were also determined. Cu(II) complexes of tinidazole brought about substantial reduction in carbohydrate and protein content in S. aureus and P. aeruginosa. Downregulation of quorum sensing signaling mechanism viz. reduced production of pyocyanin and elastase during biofilm formation was also detected. Cu(II) complexes showed much higher tendency to prevent biofilm formation than tinidazole, almost comparable to amoxicillin, an established drug in this regard.