Structure-Activity Relationship Assessment of Sophorolipid Ester Derivatives against Model Bacteria Strains.

Filbert Totsingan,Richard A Gross,Fei Liu

doi:10.3390/molecules26103021

Filbert Totsingan, Richard A Gross + Show 1 more

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https://doi.org/10.3390/molecules26103021

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Abstract

Sophorolipids (SLs) are glycolipids that consist of a hydrophilic sophorose head group covalently linked to a hydrophobic fatty acid tail. They are produced by fermentation of non-pathogenic yeasts such as Candida Bombicola. The fermentation products predominantly consist of the diacetylated lactonic form that coexists with the open-chain acidic form. A systematic series of modified SLs were prepared by ring opening of natural lactonic SL with n-alkanols of varying chain length under alkaline conditions and lipase-selective acetylation of sophorose primary hydroxyl groups. The antimicrobial activity of modified SLs against Gram-positive human pathogens was a function of the n-alkanol length, as well as the degree of sophorose acetylation at the primary hydroxyl sites. Modified SLs were identified with promising antimicrobial activities against Gram-positive human pathogens with moderate selectivity (therapeutic index, TI = EC50/MICB. cereus = 6–33). SL-butyl ester exhibited the best antimicrobial activity (MIC = 12 μM) and selectivity (TI = 33) among all SLs tested. Kinetic studies revealed that SL-ester derivatives kill B. cereus in a time-dependent manner resulting in greater than a 3-log reduction in cell number within 1 h at 2×MIC. In contrast, lactonic SL required 3 h to achieve the same efficiency.

Highlights

Bacterial resistance has spread worldwide and is causing a global health crisis, which requires a global action plan [1]
To assess the structure–activity relationship (SAR) of SLs, a family of SL-esters was synthesized from natural lactonic SL by transesterification using sodium alkoxides of different lengths (Figure 1b)
The antibacterial activity of these SL derivatives was evaluated by testing the minimum inhibitory concentration (MIC) against E. coli and several Grampositive bacteria

Summary

Introduction

Bacterial resistance has spread worldwide and is causing a global health crisis, which requires a global action plan [1]. One major concern is that the number of approved antibiotics capable of combating bacterial resistance has consistently dropped over the years [4], suggesting an urgent need for new drugs that will address this worldwide problem. In drug discovery and development, it is essential to use strategies that reduce the likelihood of new therapeutics being potential targets for the development of pathogen resistance. One of the strategies to circumvent such outcomes is to focus on membraneactive drug development. This approach is favorable since it leads to rapid pathogen eradication, multi-target effects, and activity against slow-growing bacteria [5]

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