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Updated: May 28, 2026

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines
Published on: January 3, 2018
Phosphonamidates Integrating Sterically Hindered Phenols with Membrane-Active Cations: A Redox-Activated Approach to
Elmira Gibadullina1,2, Adel Shakirov1, Margarita Neganova2,3
1Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Akad. Arbuzov St. 8, Kazan 420088, Russia.
Abstract:
A strategy to create highly effective antimicrobial agents was proposed based on the conjugation of three functional components: a cationic quaternary ammonium salt (QAS) that exerts a membrane-disrupting effect and promotes selective accumulation on bacterial surfaces; a phosphonamidate linker for controlled activation; and a sterically hindered phenol (SHP) fragment as a potential redox component. This approach enabled the preparation of 40 target phosphonamidate-SHP/QAS hybrids in high yields (88-98%). Evaluation of their antimicrobial activity against major pathogens and methicillin-resistant Staphylococcus aureus (MRSA) revealed high potency against Gram-positive bacteria. The lead compounds achieved minimum inhibitory concentration (MIC) values of 0.7-2.8 μM, which is up to 10 times lower than that of the reference drug, norfloxacin. Mechanistic studies confirmed that these hybrids disrupt the bacterial membrane. In addition, an increase in intracellular ROS levels was observed for the most active compound. The SHP/QAS hybrids retained high activity against S. aureus ATCC 209P after 17 passages and showed low cytotoxicity (SI = 62-92) and negligible hemolysis. These properties indicate that this approach may offer a useful strategy for developing antibacterial agents with a potentially lower risk of inducing conventional resistance mechanisms.
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