Studies of viomycin, an anti-tuberculosis antibiotic: copper(ii) coordination, DNA degradation and the impact on delta ribozyme cleavage activity

Abstract

Viomycin is a basic peptide antibiotic, which is among the most effective agents against multidrug-resistant tuberculosis. In this paper we provide the characteristics of its acid base properties, coordination preferences towards the Cu(ii) ions, as well as the reactivity of the resulting complexes against plasmid DNA and HDV ribozyme. Careful coordination studies throughout the wide pH range allow for the characterisation of all the Cu(ii)-viomycin complex species. The assignment of proton chemical shifts was achieved by NMR experiments, while the DTF level of theory was applied to support molecular structures of the studied complexes. The experiments with the plasmid DNA reveal that at the physiological levels of hydrogen peroxide the Cu(ii)-viomycin complex is more aggressive against DNA than uncomplexed metal ions. Moreover, the degradation of DNA by viomycin can be carried out without the presence of transition metal ions. In the studies of antigenomic delta ribozyme catalytic activity, viomycin and its complex are shown to modulate the ribozyme functioning. The molecular modelling approach allows the indication of two different locations of viomycin binding sites to the ribozyme.

Essential trace elemental levels (zinc, iron and copper) in the biological samples of smoker referent and pulmonary tuberculosis patients

“…Furthermore, these elements are considered as possible key aspects in various contagious infections. Various facts stated that a few transition elements facilitate immune system inhibit microorganisms such as Mycobacterium TB [25,26]. The ingestion of toxic elements may lead to pulmonary TB, myocardial infarctions and atherosclerosis related disorders by rising oxidative stress caused by deficiency of an antioxidant element Zinc [27].…”

Essential and toxic metals in serum of individuals with active pulmonary tuberculosis in an endemic region

“…A set of evidences indicated that some transition metals help immune system suppress microorganisms such as Mycobacterium tuberculosis. [10], [11]…”

<p>Identification of Osteosarcoma Metastasis-Associated Gene Biomarkers and Potentially Targeted Drugs Based on Bioinformatic and Experimental Analysis</p>

“…It is currently mainly used for the treatment of tuberculosis, and its anti-tumor effect has not been previously mentioned in relevant studies. 34,35 We speculate that viomycin may be used for the targeted treatment of patients with metastatic OS. Taken together, we identified a series of drugs that interact with MRSs through reverse screening, providing more potential options for the treatment of patients with metastatic OS.…”