Synthesis, biological evaluation and structure-activity relationship of 2-(2-hydroxyaryl)alkenylphosphonium salts with potency as anti-MRSA agents.

Autor: Terekhova NV; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, Kazan 420088, Russian Federation., Lyubina AP; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, Kazan 420088, Russian Federation., Voloshina AD; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, Kazan 420088, Russian Federation., Sapunova AS; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, Kazan 420088, Russian Federation., Khayarov KR; Institute of Chemistry, Kazan Federal University, Kremlevskaya Str. 18, Kazan 420008, Russian Federation., Islamov DR; Laboratory for Structural Studies of Biomacromolecules, FRC Kazan Scientific Center of RAS, Lobachevskogo Str., 2/31, Kazan 420111, Russian Federation., Usachev KS; Laboratory for Structural Studies of Biomacromolecules, FRC Kazan Scientific Center of RAS, Lobachevskogo Str., 2/31, Kazan 420111, Russian Federation., Evtugyn VG; Interdisciplinary center for Analytical microscopy, Kazan Federal University, Kremlevskaya str. 18, Kazan 420008, Russian Federation., Tatarinov DA; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, Kazan 420088, Russian Federation; Institute of Chemistry, Kazan Federal University, Kremlevskaya Str. 18, Kazan 420008, Russian Federation. Electronic address: datint@iopc.ru., Mironov VF; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, Kazan 420088, Russian Federation.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2022 Oct; Vol. 127, pp. 106030. Date of Electronic Publication: 2022 Jul 16.
DOI: 10.1016/j.bioorg.2022.106030
Abstrakt: Here we report the synthesis, in vitro antimicrobial activity, preliminary toxicity and mechanism study of a new series of 2-(2-hydroxyaryl)alkenylphosphonium salts with the variation of phosphonium moiety obtained by a two-step synthetic method from phosphine oxides. The salts showed pronounced activity against Gram-positive bacteria, including MRSA strains, and some fungi. Mechanism of action against S. aureus was studied by CV test, TEM and proteomic assay. No cell wall integrity loss was observed while proteomic assay results suggested interference in different metabolic processes of S. aureus. For this series, lipophilicity was determined as a key factor for the inhibition of Gram-positive bacteria growth and S. aureus killing. Biological properties of methylated derivatives were notably different with manifested action against Gram-negative bacteria.
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Databáze: MEDLINE
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