Poisonous pesticide transformed into treatment against antibiotic-resistant bacteria

Poisonous pesticide transformed into treatment against antibiotic-resistant bacteria


  • Post By : Kumar Jeetendra

  • Source: Immanuel Kant Baltic Federal University

  • Date: 30 Dec,2020

They are used as pesticides and fungicides. However, these substances could be poisonous to humans and cause mutations. As they aren’t frequently used, there’s little data about them in the medicinal chemistry literature. However, it has been suggested recently that the groups of substances that are traditionally avoided can help to fight pathogenic bacteria. Yet, to reduce toxic effects, a wonderful amount of work must be carried out at the molecular level, accurate optimization of the molecular environment of the nitro-heteroaromatic”warhead”.

The validity of the approach was demonstrated in the early 2000s through the evolution of anti-tuberculosis drugs delamanid and pretomanid, currently approved for medical use. They act like prodrugs, in other words, the material itself is inactive, but acquires new properties as soon as it enters the human body.

Concerning this work, scientists in the Baltic Federal University together with colleagues from St. Petersburg State University, the L. Pasteur Research Institute of Epidemiology and Microbiology, and the Research Institute of Phthisiopulmonology in St. Petersburg, are searching for new effective antibacterial drugs, studying various nitrogen heteroaromatic compounds with a nitro group which might be utilised in medicine further.

The compound OTB-021 was found to work well against drug-sensitive strains of tuberculosis pathogens, but was helpless against strains of pathogens that belong to the so-called ESKAPE panel. ESKAPE is an abbreviation for the names of bacterial species most frequently developing resistance to antibiotics: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter aerogenes. It is a sort of a pun:”eskape” sounds like”escape”, and the germs of this panel are known to be resistant to most of the antibiotics that are known, that is, they appear to”escape” from medication.

To know how to modify the chemical so that it might act on such pathogenic bacteria the scientists constructed two isomeric (identical in the atomic arrangement) series according to OTB-021. Side amino groups shifted their position to make the aromatic nitrogen-rich core of the substance more compact, this should decrease the toxicity of this substance. The sensitivity of microorganisms to a different compound was tested via disc diffusion technique. Zones of the inhibition of bacterial growth by antibiotic discs and dried solution of the chemical in Petri dishes were quantified.

The minimal concentration of the chemical that prevents the growth of germs (μg / ml) for the tested substance shows a result comparable to the use of a ml of the antibiotic ciprofloxacin: for instance, 0.3 μg / ml of an antibiotic for Enterococcus acts exactly the same as two μg / ml of one of the new substances.

Journal reference:

Chuprun, S., et al. (2020) Mutually Isomeric 2- and 4-(3-Nitro-1,2,4-triazol-1-yl)pyrimidines Inspired by an Antimycobacterial Screening Hit: Synthesis and Biological Activity against the ESKAPE Panel of Pathogens. Antibiotics. doi.org/10.3390/antibiotics9100666.

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