Fast Release of Carboxylic Acid inside Cells.

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Tác giả: Yvan Caspar, Benoit Chovelon, Sandrine Ollagnier de Choudens, Leandro J Dos Santos, Eric Faudry, Mickaël Henry, Florian C Marro, Pascal Moser, Jaione Saez Cabodevilla, Kevin Sanchez-Garcia, Yung-Sing Wong, Renaud Zelli

Ngôn ngữ: eng

Ký hiệu phân loại: 363.7386 Environmental problems

Thông tin xuất bản: Germany : ChemMedChem , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 179739

Delivering carboxylic acid functions into cells is challenging due to their poor permeability across lipophilic membranes at physiological pH, where they are ionized. Masking carboxylic acids as esters improves cell entry, but once inside the cell, its rapid release is essential to maintain spatiotemporal control which can be beneficial for therapeutic and diagnostic applications. This study evaluates the 2-hydroxyethyl-dithio-benzyl ester functional group which undergoes selective and rapid cleavage of the disulfide bond by thioredoxin (Trx), triggering rapid self-immolation of the thio-benzyl ester releasing the carboxylic acid. Fluorescence-based assays using the pro-fluorescent BODIPY structure have demonstrated the rapid intracellular release of carboxylic acids within minutes in both eukaryotic and prokaryotic cells. The approach was tested on antibiotics, and among them, levofloxacin ester prodrug, having the 2-hydroxyethyl-dithio-benzyl ester functional group, showed significantly enhanced antimicrobial activity against resistant and intracellular bacteria compared to its methyl ester analogue.
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