New Ianthelliformisamine Derivatives as Antibiotic Enhancers against Resistant Gram-Negative Bacteria

Cyril Pieri , Diane Borselli (1) , Carole Di Giorgio (2) , Michel de Meo (2) , Jean-Michel Bolla (1) , Nicolas [e-mail] Vidal (3) , Sébastien Combes (3) , Jean Michel Brunel (4)

1 TMCD2 - Transporteurs membranaires, chimioresistance et drug-design
2 IMBE - Institut méditerranéen de biodiversité et d'écologie marine et continentale
3 ICR - Institut de Chimie Radicalaire
4 CRCM - Centre de Recherche en Cancérologie de Marseille

A series consisting of ianthelliformisamimes A, B, and C as well as its synthetic analogues was prepared in high chemical yield, from 27 to 91%, using peptide coupling as the key step, and the compounds were evaluated for their in vitro antibiotic enhancer properties against resistant Gram-negative bacteria and clinical isolates. The mechanism of action of one of these derivatives against Pseudomonas aeruginosa when combined with doxycycline was precisely evaluated utilizing bioluminescence to measure ATP efflux and fluorescence to evaluate membrane depolarization.

Domaines: Chimie

Cyril Pieri, Diane Borselli, Carole Di Giorgio, Michel de Meo, Jean-Michel Bolla, et al.. New Ianthelliformisamine Derivatives as Antibiotic Enhancers against Resistant Gram-Negative Bacteria. Journal of Medicinal Chemistry, 2014, 57 (10), pp.4263--4272. ⟨10.1021/jm500194e⟩. ⟨hal-01460535⟩