The widespread use of antibiotics in recent decades has been a major factor in the emergence of antibiotic resistances. Antibiotic-resistant pathogens pose increasing challenges to healthcare systems in both developing and developed countries. To counteract this, the development of new antibiotics or adjuvants to combat existing resistance to antibiotics is crucial. Glycomimetics, for example carbasugars, offer high potential as adjuvants, as they can inhibit metabolic pathways or biofilm formation due to their similarity to natural substrates. Here, we demonstrate the synthesis of carbasugar precursors (CSPs) and their application as biofilm inhibitors for E. coli and MRSA, as well as their synergistic effect in combination with antibiotics to circumvent biofilm-induced antibiotic resistances. This results in a biofilm reduction of up to 70% for the CSP rac-7 and a reduction in bacterial viability of MRSA by approximately 45% when combined with the otherwise ineffective antibiotic mixture of penicillin and streptomycin.
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http://dx.doi.org/10.1038/s41598-022-22807-8 | DOI Listing |
Sci Rep
October 2022
Institute of Precision Medicine, Furtwangen University, Jakob-Kienzle-Strasse 17, 78054, Villingen-Schwenningen, Germany.
The widespread use of antibiotics in recent decades has been a major factor in the emergence of antibiotic resistances. Antibiotic-resistant pathogens pose increasing challenges to healthcare systems in both developing and developed countries. To counteract this, the development of new antibiotics or adjuvants to combat existing resistance to antibiotics is crucial.
View Article and Find Full Text PDFJ Org Chem
November 2022
Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China.
A new synthetic strategy for C7-carbasugars is developed via an intramolecular Morita-Baylis-Hillman reaction, in which a substituted dial precursor prepared from d-mannose cyclizes smoothly in the presence of DMAP to afford polyhydroxylated cyclohex-1-enecarbaldehyde with good yield. By employment of the cyclization products as key intermediates, the first syntheses of carbasugar ester and epicorepoxydon A, as well as practical syntheses of epoxydines B and C, (-)-MK7607, (-)-streptol, and (-)-gabosine E are achieved.
View Article and Find Full Text PDFOrg Biomol Chem
April 2019
Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China.
Gabosines and their natural analogues, belonging to C7 carbasugars, have attracted great attention in synthesis due to their rich structural variety and promising biological activities. A new diversity-oriented approach for the gabosine-type carbasugars based on a tunable regioselective aldol cyclization of flexible precursor 2 is explored. Two cyclization modes (A and B) of the precursor can be well controlled by switching promoters to selectively produce two resulting cyclohexa(e)nones 3 and 10, both of which are versatile intermediates for various C7 carbasugars.
View Article and Find Full Text PDFChin J Nat Med
October 2017
State Key Laboratory of Microbial Metabolism, School of Life Science & Biotechnology and Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:
Valienone is a significant natural carbasugar member of the C7-cyclitol family as a valuable precursor for glycosidase inhibitor drugs. It is an intermediate of validamycin A biosynthesis pathway and exhibits minimal accumulation in the fermentation broth of the natural Streptomyces producer. A quantitative analytical method is crucial for the development of a breakthrough microbial process overcoming the consumption of the natural metabolic flux.
View Article and Find Full Text PDFCarbohydr Res
June 2016
Department of Chemistry, Hunter College and The Graduate Center of the City University of New York, New York, NY 10016, USA. Electronic address:
The synthesis of β-carba-xylo and arabino pyranosides of cholestanol is described. The synthetic strategy, which is analogous to the Postema approach to C-glycosides, centers on the ring closing metathesis of an enol ether-alkene precursor to give a cyclic enol ether that is elaborated to a carba-pyranoside via hydroboration-oxidation on the olefin. The method, which is attractive for its modularity and stereoselectivity, may find wider applications to carba-hexopyranosides and other complex cycloalkyl ether frameworks.
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