Trialkyl(vinyl)phosphonium Chlorophenol Derivatives as Potent Mitochondrial Uncouplers and Antibacterial Agents.

Autor: Terekhova NV; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of Russian Academy of Sciences, Arbuzov Str. 8, Kazan 420088, Russian Federation., Khailova LS; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russian Federation., Rokitskaya TI; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russian Federation., Nazarov PA; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russian Federation., Islamov DR; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of Russian Academy of Sciences, Arbuzov Str. 8, Kazan 420088, Russian Federation., Usachev KS; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya 18, Kazan 420008, Russian Federation., Tatarinov DA; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of Russian Academy of Sciences, Arbuzov Str. 8, Kazan 420088, Russian Federation., Mironov VF; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of Russian Academy of Sciences, Arbuzov Str. 8, Kazan 420088, Russian Federation., Kotova EA; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russian Federation., Antonenko YN; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russian Federation.
Jazyk: angličtina
Zdroj: ACS omega [ACS Omega] 2021 Jul 29; Vol. 6 (31), pp. 20676-20685. Date of Electronic Publication: 2021 Jul 29 (Print Publication: 2021).
DOI: 10.1021/acsomega.1c02909
Abstrakt: Trialkyl phosphonium derivatives of vinyl-substituted p -chlorophenol were synthesized here by a recently developed method of preparing quaternary phosphonium salts from phosphine oxides using Grignard reagents. All the derivatives with a number ( n ) of carbon atoms in phosphonium alkyl substituents varying from 4 to 7 showed pronounced uncoupling activity in isolated rat liver mitochondria at micromolar concentrations, with a tripentyl derivative being the most effective both in accelerating respiration and causing membrane potential collapse, as well as in provoking mitochondrial swelling in a potassium-acetate medium. Remarkably, the trialkyl phosphonium derivatives with n from 4 to 7 also proved to be rather potent antibacterial agents. Methylation of the chlorophenol hydroxyl group suppressed the effects of P 555 and P 444 on the respiration and membrane potential of mitochondria but not those of P 666 , thereby suggesting a mechanistic difference in the mitochondrial uncoupling by these derivatives, which was predominantly protonophoric (carrier-like) in the case of P 555 and P 444 but detergent-like with P 666 . The latter was confirmed by the carboxyfluorescein leakage assay on model liposomal membranes.
Competing Interests: The authors declare no competing financial interest.
(© 2021 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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