Sesquiterpene Lactones from Cotula cinerea with Antibiotic Activity against Clinical Isolates of Enterococcus faecalis.

Alessio Cimmino,Chakali Gahdab,Marco Masi,Maria Rosaria Catania,Antonio Evidente,Emanuela Roscetto,Imene Radjai,Angela Tuzi,Rossella Paolillo,Amedeo Guarino

doi:10.3390/antibiotics10070819

Alessio Cimmino, Chakali Gahdab + Show 8 more

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https://doi.org/10.3390/antibiotics10070819

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Abstract

Cotula cinerea, belonging to the tribe Anthemideae, is a plant widespread in the Southern hemisphere. It is frequently used in folk medicine in North African countries for several of its medical properties, shown by its extracts and essential oils. The dichloromethane extract obtained from its aerial parts demonstrated antibiotic activity against Enterococcus faecalis and was fractionated by bioguided purification procedures affording five main sesquiterpene lactones. They were identified by spectroscopic methods (NMR and ESIMS data) as guaiantrienolides, i.e., 6-acetoxy-1β-,6-acetoxy-1α-, and 6-acetoxy-10-β-hydroxyguaiantrienolide (1–3), and germacrenolides, i.e., haagenolide and 1,10-epoxyhaagenolide (4 and 5). The absolute configuration was assigned by applying the advanced Mosher’s method to haagenolide and by X-ray diffraction analysis to 1,10-epoxyhaagenolide. The specific antibiotic and antibiofilm activities were tested toward the clinical isolates of Enterococcus faecalis. The results showed that compounds 3–5 have antibacterial activity against all the strains of E. faecalis, while compound 2 exhibited activity only toward some strains. Compound 1 did not show this activity but had only antibiofilm properties. Thus, these metabolites have potential as new antibiotics and antibiofilm against drug resistant opportunistic pathogens.

Highlights

There has been remarkable interest in the last twenty years in the discovery of natural substances as a potential reservoir of innovative therapeutic solutions for human health, with the prospect of integrating and sometimes replacing conventional drugs
There is a growing interest in the study of natural substances extracted from plants to counter the galloping phenomenon of antibiotic resistance, i.e., the development and spread of microorganisms resistant to the drugs used in anti-infective therapies [1,2,3,4]
The organic extracts of C. cinerea obtained using different solvents as detailed in Section 3 were assayed at a single high concentration on Staphylococcus aureus ATCC 29231, Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii ATCC 747 by standard broth microdilution assay to test the bacterial growth inhibition

Summary

Introduction

There has been remarkable interest in the last twenty years in the discovery of natural substances as a potential reservoir of innovative therapeutic solutions for human health, with the prospect of integrating and sometimes replacing conventional drugs. Over the last few decades, antibiotic resistance (AR) has become a global threat to health systems and public health around the world. If it cannot be effectively counteracted, it is estimated that by 2050 the spread of multidrug-resistant strains will hamper the control of many infectious diseases, undermining the achievements of modern medicine [5]. The first is that following the introduction of a new antibiotic, resistance to it will arise sooner or later; the second is the growing gap between the increase in antimicrobial resistance and the development of new compounds. This means that the pace of discovery and development of new antibiotics is slower than the emergence and spread of resistance mechanisms among bacteria, which are able to respond rapidly to selective pressures and pass resistance genes to the offspring

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