Conjugates of monocyclic β-lactams and siderophore mimetics : a patent evaluation (WO2023023393)

Krajnc, Alen (author), Gobec, Stanislav (author)

Introduction: β-Lactams, which include monobactams, remain the most important class of antibiotics worldwide. Aztreonam, the only monobactam in clinical use, has remarkable activity against many Gram-negative bacteria, but limited activity against some of the most problematic multidrug-resistant (MDR) pathogens, such as MDR Pseudomonas aeruginosa and Acinetobacter baumannii co-expressing extended-spectrum- and metallo-β-lactamases, which can inactivate aztreonam by hydrolysis. Areas covered: Structurally novel siderophore-conjugated aztreonam derivatives with improved antibacterial properties against several high-priority pathogens are claimed. This invention reports that sidechain extension of aztreonam is tolerated; the coupling of its aminothiazoloxime carboxylic acid part with a siderophore mimetic significantly improved the antibacterial activity against several problematic strains, including MDR A. baumannii isolates with carbapenemase/cephalosporinase activity. Expert Opinion: Finding new strategies to tackle bacterial resistance to β-lactam antibiotics is critical. Considering that β lactams are validated and safe drugs, this research may stimulate the field to develop new ideas in the arena of antimicrobial drug discovery, particularly with respect to siderophore mimetics.

• Language: English
• Keywords: antimicrobial resistance, conjugates, aztreonam, anticoagulant, β-lactams, monocyclic β-lactams, siderophores
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: Str. 471-476
• Numbering: Vol. 33, no. 7-8
• PID: 20.500.12556/RUL-152245
• UDC: 615.015.8
• ISSN on article: 1354-3776
• DOI: 10.1080/13543776.2023.2262135
• COBISS.SI-ID: 171047171
• Publication date in RUL: 14.11.2023

Record is a part of a journal

• Title: Expert opinion on therapeutic patents
• Shortened title: Expert opin. ther. pat.
• Publisher: Taylor & Francis
• ISSN: 1354-3776
• COBISS.SI-ID: 15313959

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: protimikrobna odpornost, aztreonam, konjugati, β-laktami, monociklični β-laktami, siderofori, bakterijska rezistenca, farmacevtska kemija