Development of Naphthalene-Derivative Bis-QACs as Potent Antimicrobials: Unraveling Structure–Activity Relationship and Microbiological Properties

Development of Naphthalene-Derivative Bis-QACs as Potent Antimicrobials: Unraveling Structure–Activity Relationship and Microbiological Properties Full article

Journal

Molecules
ISSN: 1420-3049

Output data

Year: 2024, Volume: 29, Number: 23, Article number : 5526, Pages count : DOI: 10.3390/molecules29235526

Authors

Frolov Nikita A. ¹ , Seferyan Mary A. ¹ , Detusheva Elena V. ² , Son Elizabeth ² , Kolmakov Ilya G. ^3,1 , Kartseva Alena S. ² , Firstova Victoria V. ² , Vereshchagin Anatoly N. ¹ , Elinson Michail N. ¹

Affiliations

1	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow, Russia
2	State Research Center for Applied Microbiology and Biotechnology, Obolensk, 142279 Serpukhov, Russia
3	Faculty of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia

While the pandemic is behind us, the world community faces a global threat of bacterial resistance outbreak. One of the key ways to combat the spread of multi-resistant bacteria is infection prevention and control tactics using modern antiseptic and disinfectant compositions. Herein, we continue the path to unravel the structure–activity relationship (SAR) of potent pyridine-derived biocide class bis-quaternary ammonium compounds (QACs). In this study, twenty dihydroxynaphthalene-derivative bis-QACs were subjected to extensive microbiological analysis on planktonic cells and biofilms of the ESKAPE microorganisms. Among them, hit compounds were superior in their bacteriostatic and bactericidal action to commercial mono-QACs and were comparable to the best bis-QAC antiseptic on the market. SAR analysis indicated that the linker conformation does not significantly affect the activity, though structure symmetry and especially lipophilicity had an influence on antibacterial performance. Furthermore, we delve deeper in investigation of the antimicrobial potential of bis-QACs and conducted a variety of assays, including time–kill kinetics, bacterial resistance formation, cell morphology, and cytotoxicity. Studies showed promising results for compounds 5d and 6d, indicating 2 to 3-fold less cytotoxicity and hemotoxicity compared to commercial QACs. Moreover, SEM imaging revealed that bis-QACs can cause severe membrane damage to S. aureus and P. aeruginosa strains, confirming great potential of novel compounds as antiseptic and disinfectant.

Frolov N.A. , Seferyan M.A. , Detusheva E.V. , Son E. , Kolmakov I.G. , Kartseva A.S. , Firstova V.V. , Vereshchagin A.N. , Elinson M.N.
Development of Naphthalene-Derivative Bis-QACs as Potent Antimicrobials: Unraveling Structure–Activity Relationship and Microbiological Properties
Molecules. 2024. V.29. N23. 5526 . DOI: 10.3390/molecules29235526 WOS OpenAlex

Web of science:	WOS:001376543700001
OpenAlex:	W4404633388

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