On the substance of the case: new antibiotics with anti-cancer properties have been created in the Russian Federation

Russian chemists have developed a new method for producing derivatives of the popular antimicrobial and antifungal substance imidazole with antibacterial properties. The authors used commercially available compounds as starting reagents, and the proposed method is environmentally friendly and does not lead to the formation of by-products that would require additional purification. As experts emphasize, synthesized drugs can be used as remedies for persistent hospital infections, they can also be used against tumors and as antidepressants.

Imidazole and its derivatives

Scientists from St. Petersburg State University and the St. Petersburg Scientific Research Institute of Epidemiology and Microbiology named after Pasteur have developed an innovative method for synthesizing hard-to-reach derivatives. It is based on the use of available compounds — guanidines and isocyanides, which in the presence of oxygen and a nickel catalyst are converted exclusively into the desired compounds.

This method is environmentally friendly because it does not use toxic oxidizing agents. Instead, atmospheric oxygen participates in the reaction, and the only by—product is water. This process can also be carried out in two ways: either by heating or under the influence of ordinary visible light.

Photo: IZVESTIA/Anna Selina

Chemists have also studied the reaction mechanism — the sequence of steps that lead to chemical transformation. This allowed them to optimize synthesis conditions and achieve a high conversion efficiency of 97%.

— The developed approach allows efficient synthesis of previously difficult-to-obtain imidazole derivatives and opens up prospects for the creation of new pharmaceutically active substances. The compounds obtained exhibit high antibacterial activity against a wide range of infectious disease pathogens, the treatment of which is complicated by rapidly developing antibiotic resistance," Svetlana Katkova, project manager, Candidate of Chemical Sciences, Associate Professor of the Department of Physical Organic Chemistry at St. Petersburg State University, told Izvestia.

Which bacteria do the new antibiotics work against

The researchers tested the antibacterial properties of the compounds obtained by exposing them to cultures of Gram-negative and Gram-positive bacteria such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter. These microbes often cause nosocomial infections, including pneumonia, urinary tract infections, digestive tract infections, etc.

All tested compounds showed significant antibacterial activity against a wide range of pathogens. The minimum dose required to stop bacterial growth was less than 1.5 micrograms per milliliter, which is comparable to the effectiveness of antibiotics used in medical practice.

Photo: IZVESTIA/Sergey Lantyukhov

At a time when microbial resistance to antibiotics is growing all over the world, it is important to obtain any new substances that can become antibiotics. The demand for imidazoles in this regard is no exception, said Alexander Lavrishchev, a therapist at the Semeynaya clinic. The problem with imidazoles was that all known drugs that are currently based on these compounds are antifungal agents. The discovery of new ways to synthesize imidazole compounds will help create new drugs that are effective against bacteria.

— A new synthesis method makes it possible to obtain many different imidazole-based compounds, each of which can become a new drug. And, by the way, it's not necessarily an antibiotic, perhaps they will have other properties discovered, which is good news, as well as the environmentally friendly method of such synthesis," the expert said.

Photo: Stefania Kolesnikova

Among the bacteria against which imidazole derivatives were tested, there are dangerous pathogens of infections that occur in the case of immunodeficiency in the patient. For example, in HIV infection, organ transplantation, in children with genetic defects of the immune system, in cancer patients receiving treatment with certain chemotherapeutic drugs.

— The search for new and more effective ways to synthesize imidazoles and their derivatives is extremely important, since many strains of existing microorganisms acquire antibiotic resistance. This is important, for example, for patients with hospital infections," said Albert Rizvanov, Head of the Center for Excellence "Personalized Medicine" at Kazan (Volga Region) Federal University, Corresponding member of the Academy of Sciences of the Republic of Tatarstan.

Research results, supported by a grant from the Russian Science Foundation, published in the journal ChemMedChem.