Indole-3-Acetamido-Polyamines as Antimicrobial Agents and Antibiotic Adjuvants

被引：4

作者：

Sue, Kenneth ^{[1
]}

Cadelis, Melissa M. ^{[1
,2
]}

Gill, Evangelene S. ^{[1
]}

Rouvier, Florent ^{[3
]}

Bourguet-Kondracki, Marie-Lise ^{[4
]}

Brunel, Jean Michel ^{[3
]}

Copp, Brent R. ^{[1
]}

机构：

[1] Univ Auckland, Sch Chem Sci, Private Bag 92019, Auckland 1142, New Zealand

[2] Univ Auckland, Sch Med Sci, Private Bag 92019, Auckland 1142, New Zealand

[3] Aix Marseille Univ, Inst Natl St & Rech Med INSERM, Membranes & Cibles Therapeut MCT, IRD, 27 bd Jean Moulin, F-13385 Marseille, France

[4] Museum Natl Hist Nat, Lab Mol Commun & Adaptat Microorganismes, UMR CNRS 7245, UMR 7245, 57 Rue Cvier,CP 54, F-75005 Paris, France

来源：

BIOMOLECULES | 2023年 / 13卷 / 08期

基金：

英国惠康基金;

关键词：

indole-3-acetamide; potentiator; antimicrobial; polyamine; antibiotics; antifungal agents; structure-activity relationships;

D O I：

10.3390/biom13081226

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The widespread incidence of antimicrobial resistance necessitates the discovery of new classes of antimicrobials as well as adjuvant molecules that can restore the action of ineffective antibiotics. Herein, we report the synthesis of a new class of indole-3-acetamido-polyamine conjugates that were evaluated for antimicrobial activities against a panel of bacteria and two fungi, and for the ability to enhance the action of doxycycline against Pseudomonas aeruginosa and erythromycin against Escherichia coli. Compounds 14b, 15b, 17c, 18a, 18b, 18d, 19b, 19e, 20c and 20d exhibited strong growth inhibition of methicillin-resistant Staphylococcus aureus (MRSA) and Cryptococcus neoformans, with minimum inhibitory concentrations (MIC) typically less than 0.2 mu M. Four analogues, including a 5-bromo 15c and three 5-methoxyls 16d-f, also exhibited intrinsic activity towards E. coli. Antibiotic kill curve analysis of 15c identified it to be a bactericide. While only one derivative was found to (weakly) enhance the action of erythromycin against E. coli, three examples, including 15c, were found to be strong enhancers of the antibiotic action of doxycycline against P. aeruginosa. Collectively, these results highlight the promising potential of alpha,omega-disubstituted indole-3-acetamido polyamine conjugates as antimicrobials and antibiotic adjuvants.

引用

页数：26