Y.A. Plotnikova1, E.S. Barysheva2, Peshkov S.A.3

1–3 Orenburg State University (Orenburg, Russia)

As a result of the conducted studies, it was found that the antibacterial activity may be due to both a possible synergistic effect between interacting complexes of secondary metabolites and antibiotics, and individual mechanisms inherent in a specific active agent present in the extract. At the same time, the antibacterial effect shown by the complex interaction of antibiotics and plant extracts to specific nitrogen- or phenol-containing compounds depends on the external conditions of interaction (environment, temperature, pressure, humidity, etc., and internal factors (changes in the conformations of interaction, reaction conditions, etc.)

The probability of synergistic interaction was estimated by modeling the complexes "antibiotic + secondary metabolite" in the in silico experiment in the Autodock program. The analysis of the molecular-electrostatic potential and the distribution of electron density allowed us to obtain several of the most successful intermolecular complexes, the probability of formation of which would be the greatest.

As a result of the conducted research, it was established:

1. Biochemical interaction of complexes of plant extracts and their secondary metabolites with antibiotics in vitro revealed synergistic effects against S.aureus isolates from the complexes Dianthus, Herba Achilleae millefolii, Nerba Nuregisi and Sortex Quercus (complex "tinctures + antibiotics"). However, for these extracts, no inhibition was observed in the interaction of antibiotics with secondary metabolites.

A noticeable synergistic effect was observed in Urticae folia and Camellia sinensis complexes (both in the case of tinctures and secondary metabolites). It should also be noted the synergism of combinations with Allium sativum ("antibiotics + secondary metabolites").

With respect to P.aeruginosa isolates, manifestations of synergistic effects were noted with respect to all extracts, with a difference in agents. So for Dianthus it is a combination of antibiotics with secondary metabolites. At the same time, tinctures separately, and tinctures in combination with antibiotics did not manifest themselves in any way. For Herba Achilleae millefolii, a synergistic effect was obtained in combinations of "antibiotics + tinctures" and "antibiotics + secondary metabolites". Similar results were found in Nerba Nuregisi, Urticae folia, Camellia sinensis, Folia Eucalypti viminalis, Sorbus aucuparia L. and Allium sativum. In an experiment with Sorbus aucuparia L., combinations of "antibiotic + secondary metabolites" are characterized by an additive effect rather than a synergistic one.

2. The presence in the composition of secondary metabolites of compounds such as rutin (Nerba Nuregisi, Folia Eucalypti viminalis), gallic acid (Nerba Nuregisi, Camellia sinensis, Sortex Quercus), thymol (Urticae folia, Herba Achilleae millefolii,Camellia sinensis, Sorbus aucuparia L, Dianthus), reveals the mechanism of action that explains the nature of occurrences antibacterial effect.

3. The evaluation of the molecular-electrostatic potential and interaction energies obtained by computer modeling in the in silico experiment in the Autodock program allowed us to determine the nucleophilicity of rutin and thymol, as well as ceftazidime and fosfomycin, and also to assume the most probable conformations of their interactions.

4. The analysis of IR spectra indicated the absence of chemical interactions between antibacterial agents and secondary metabolites, as indicated by the absence of additional peaks on the maps of reaction products. The key frequencies of secondary metabolites are on the same bands and are clearly visible in the spectra of extracts. The absorption bands in antimicrobials almost coincide with the absorption bands in secondary metabolites, however, in extracts, when co-administered into the medium, they are not noticeable against the background. Consequently, antibiotics in solution can form only intermolecular complexes.

Plotnikova Y.A., Barysheva E.S., Peshkov S.A. Chemical modification of antimicrobial complexes with organic molecules in order to obtain mixed ligand anti-resistant agents. Technologies of Living Systems. 2023. V. 20. № 2. Р. 42-52. DOI: https://doi.org/10.18127/ j20700997-202302-05 (In Russian)

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