Polyamino geranic derivatives as new chemosensitizers to combat antibiotic resistant Gram-negative bacteria

• Published in: Bioorganic & medicinal chemistry Vol. 21; no. 5; pp. 1174 - 1179
• Main Authors: Brunel, Jean Michel, Lieutaud, Aurélie, Lome, Vincent, Pagès, Jean-Marie, Bolla, Jean-Michel
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.03.2013; Elsevier
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotic; Antibiotic resistance; Antibiotics; Biochemistry & Molecular Biology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Data processing; Drug Resistance, Bacterial - drug effects; Efflux pump; Geranic acid derivatives; Gram-negative bacteria; Gram-Negative Bacteria - drug effects; Life Sciences & Biomedicine; mechanism of action; Microbial Sensitivity Tests; Multi-drug resistance; Pharmacology & Pharmacy; Physical Sciences; Polyamines; Science & Technology; Structure-Activity Relationship; Terpenes - chemical synthesis; Terpenes - chemistry; Terpenes - pharmacology; transporters; Triazoles - chemistry; Antibiotic; Multi-drug resistance; Geranic acid derivatives; Gram-negative bacteria; Polyamines; Efflux pump; PORIN; EFFLUX PUMPS; DRUG-RESISTANCE; MULTIDRUG-RESISTANCE
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2012.12.030

Decrease of chloramphenicol and nalidixic acid resistance in the presence of these derivatives against MDR Gram-negative strains by 4- to 64-fold. Benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate reagent (BOP) serves as an efficient and versatile coupling reagent for the design and synthesis of new polyamino geranic acid derivatives in moderate to good chemical yields varying from 47% to 83%. These compounds induced a significant decrease of antibiotic resistance in two Gram-negative bacterial MDR strains. Our data suggested that their mechanism of action is closely associated with the inhibition of the efflux pumps.