Improving the synthesis of hemin derivatives and their effect on bacterial biofilms

Autor: Sergey V. Blagodarov, Galina A. Zheltukhina, Yuliya M. Romanova, Natalia V. Alekseeva, Lyudmila D. Iskhakova, Maria I. Semashko, Eteri R. Tolordava, Vladimir E. Nebolsin
Rok vydání: 2022
Předmět:
Zdroj: Journal of Porphyrins and Phthalocyanines. 26:242-252
ISSN: 1099-1409
1088-4246
DOI: 10.1142/s1088424622500079
Popis: The emergence of antibiotic-resistant bacterial strains has recently resulted in a large focus on designing new antimicrobial agents, including those based on natural compounds. We have previously synthesized two disubstituted arginine-containing derivatives of hemin (HD) (4) and (5) that demonstrated pronounced antimicrobial activity against planktonic cells in vitro [1, 2]. These HDs are leading and promising for the creation of antibacterial agents on their basis. This research is aimed at improving the synthesis of HDs (4) and (5) to increase their yield, simplify the process and minimize the side reactions, as well as to establish their antimicrobial and destructive effect on biofilms, including those consisting of antibiotic-resistant bacteria. As a result, we were able to increase the yields of the protected dipeptide of ZArg(Z[Formula: see text]SerNH2 (3) and the corresponding HD (4) up to 97 and 93%, respectively, and also to minimize the side reaction of the formation of ornithine-containing HD. For the arginine amide modified HD (5), we have also proposed an improved synthesis scheme. The ability of HD to cause the bacteria death in the composition of formed biofilms, including those consisting of resistant bacteria, was shown. After the effect of HDs on the biofilm at concentrations of 80 and 100 [Formula: see text]g/ml, the CFU decrease was 3–5/ml. The fluorescent microscopy confirmed the bacteria mortality in the biofilm. Electron microscopy showed structural damage (fragmentation) of the formed bacterial biofilm under the effect of HDs.
Databáze: OpenAIRE
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