Chemoinformatic study of spiramycin in comparison with other antibiotics

Background. Antibiotics have different spectra of action on bacterial pathogens, including their antibiotic-resistant strains. Establishing the spectra of action of antibiotics and mechanisms of resistance to them is an important task for finding effective and safe antibiotic therapy.

Objective: a chemoinformatic study of the macrolide spiramycin in comparison with moxifloxacin, josamycin, azithromycin and clarithromycin.

Material and methods. The analysis was carried out using modern data analysis methods (theories of labeled graph analysis, metric data analysis, combinatorial solvability theory, topological theory of ill-formalized problem analysis) developed within the framework of the algebraic approach to recognition.

Results. Chemomicrobiome and pharmacoinformatic profiling of spiramycin indicated significant differences between the spiramycin molecule and the comparison molecules in terms of efficacy, safety and mechanisms of action. Characteristic features of spiramycin action were inhibition of protein synthesis by influencing the ribosome, with possible inhibition of bacterial topoisomerase, DNA synthesis and with anti-membrane activity, including through ionophore mechanisms. Analysis of correlations between chemogenomic profiles of molecules indicated a pronounced similarity of the effects of three of the five studied molecules (josamycin, azithromycin, clarithromycin) with a significant difference in the effects of spiramycin from the effects of other studied macrolides. Mechanisms of resistance to spiramycin potentially include genes from the functional groups “assembly of the outer membrane of gram-negative bacteria”, “sorbitol transport”, “transmembrane transporter of L-leucine” etc. Spiramycin was characterized by the best safety profile in terms of “antimicronutrient” effects (increase in the risk of excretion of a particular micronutrient by only 7%).

Conclusion. The significant difference between the chemogenomic, chemomicrobiomic and pharmacoinformatic profiles of spiramycin and other antibiotics (including other macrolides) suggests low resistance to spiramycin at the population level.

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