Design,Synthesis And Bacterial Screening Studies Of Ferrichrome Analogue-Fluorescent Probes

Bacteria resistance is getting worse and worse,and the development of new antibiotics against drug-resistant bacteria is urgent.In the new antibiotics currently developed,siderophore antibiotics have unique advantages.The active transport system of siderophore-Fe³⁺complex can enhance the drug concentration inside bacteria to exert antibacterial effects.This is very effective in addressing the bacterial resistance problem caused by bacterial drug efflux pumps or the decreased permeability of the bacterial outer membrane.Albomycins are natural siderophore antibiotics,which were used by the former Soviet Union to treat children with pneumonia,meningitis,and other clinical diseases.Taking advantage of its siderophore-ferrichrome analogue structure to develop new siderophore antibiotics is promising.While,regrettably,there are no clear reports on the ferrichrome analogue for bacteria.It’s not conducive to the development of siderophore antibiotics based on ferrichrome analogue,and limits the development of new siderophore antibiotics.It would be significant to understand the selectivity of ferrichrome analogue for various bacteira.To study the bacterial selectivity range of ferrichrome analogue,seven fluorescent probes were designed and synthesized.The ferrichrome analogue was connected with seven fluorescent molecules through a triethylene glycol linker 2-20.Then,the seven probes were tested for their ability to enter twelve bacteria under iron-limitted conditions.Screening results of probes show that,for different fluorescent probes,the uptake of bacteria is different.Under iron-limitted conditions,A.baumannii 1345,Y.enterocolitica ATCC 23715,E.coli.ATCC 11775,E.faecium B148,and S.pneumoniae ATCC 49619 uptake ferrichrome analogue-fluorescent analogues,which could serve as a guide to design ferrichrome analogue-based Trojan Horse antibiotics.