The actual problem in medicine is a phenomenon of antibiotic resistance, therefore, it is expedient to develop and introduce new antibiotics or to improve the transport of already known antibiotics into the cell. PEGylating is the one of the most successful ways of improving of the delivery of therapeutic molecules to the cell, such as proteins, oligonucleotides and other biomolecules. Thus, it is promising to introduce PEG fragments into the structure of antibiotics with the preservation of their biological activity.
The object of research is enrofloxacin, an antibiotic of the third generation of fluoroquinolones, that are derivatives of 4-quinolone and contain a piperazine ring and a fluorine atom. The presence of fluorine atom in their structure substantially expands the spectrum of their antibacterial activity. Enrofloxacin is successfully used in veterinary medicine for the treatment of many bacterial diseases, but due to the rapid increase in the resistance of microorganisms to the action of antibiotic, the development of new antibiotics based on enrofloxacin is relevant. The presence of a reactive carboxyl group in the molecule of the antibiotic makes it possible to modify its structure for obtaining new compounds.
During the development of the method for the modified enrofloxacin production, the following reactions were considered: straight esterification of carboxyl groups, esterification using Steglich reaction and obtaining esters through the intermediate formation of chloranhydride. The yield of PEGylated product in straight esterification and using Steglich reaction did not exceed 20-25%, therefore the synthesis of PEGylated enrofloxacin is proposed through the intermediate formation of its chloranhydride. During the reaction the formation of PEGylated enrofloxacin was monitored by IR spectroscopy. The purity of the products according to the data of high-performance liquid chromatography was 98%.
It is important for such a modification that the obtained PEGylated enrofloxacin hadn`t, at least, less bactericidal properties than the original antibiotic. Antibacterial activity of PEGylated compounds was investigated by serial dilutions using Pseudomonas aeruginosa culture. It is shown that antibacterial activity of the enrofloxacin compounds covalently coupled to polyethylene glycol are higher in comparison with the initial antibiotic.
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