Macrolides are a diverse class of hydrophobic compounds characterized by a macrocyclic lactone ring and distinguished by variable side chains/groups. Some of the most well characterized macrolides are toxins produced by marine bacteria, sea sponges, and other species. Many marine macrolide toxins act as biomimetic molecules to natural actin-binding proteins, affecting actin polymerization, while other toxins act on different cytoskeletal components. The disruption of natural cytoskeletal processes affects cell motility and cytokinesis, and can result in cellular death. While many macrolides are toxic in nature, others have been shown to display therapeutic properties. Indeed, some of the most well known antibiotic compounds, including erythromycin, are macrolides. In addition to antibiotic properties, macrolides have been shown to display antiviral, antiparasitic, antifungal, and immunosuppressive actions. Here, we review each functional class of macrolides for their common structures, mechanisms of action, pharmacology, and human cellular targets.
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http://dx.doi.org/10.3390/toxins13050347 | DOI Listing |
Background: The most severe complications of antibiotic use are clostridial infection (CDI) and pseudomembranous colitis (PMC). There is a need for further study of these conditions and identification of their triggers.
Aim: To identify risk factors for severe forms of antibiotic-associated diarrhea caused by .
Toxins (Basel)
December 2024
Hebei Key Laboratory of Crop Stress Biology, Hebei Normal University of Science and Technology, Qinhuangdao 066004, China.
is the main pathogen of peanut pod rot in China. To investigate the type of toxin and its pathogenic mechanism, a macrolide, brefeldin A, was isolated. The structure of the compound was identified by 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS).
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December 2024
Department of Chemistry, University of Ghana, Legon-Accra P.O. Box LG56, Ghana.
Mycolactone is a complex macrolide toxin produced by , the causative agent of Buruli ulcer. The aim of this paper is to review the chemistry, biosynthetic, and synthetic pathways of mycolactone A/B to help develop an understanding of the mode of action of these polyketides as well as their therapeutic potential. The synthetic work has largely been driven by the desire to afford researchers enough (≥100 mg) of the pure toxins for systematic biological studies toward understanding their very high biological activities.
View Article and Find Full Text PDFChem Res Toxicol
December 2024
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
The algal macrolide goniodomin A (GDA) undergoes ring-cleavage under unusually mild, alkaline conditions to form mixtures of stereoisomers of seco acids GDA-sa and iso-GDA-sa. In the primary fragmentation pathway, opening of the macrolide ring occurs by displacement of the carboxyl group by a base-catalyzed attack of the C32 hemiketal hydroxy group on C31, yielding an oxirane-carboxylic acid, named goniodomic acid. The oxirane ring is unstable, undergoing solvolytic opening to form mainly GDA-sa.
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December 2024
Department of Pharmacy, Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Background: Microbiota-derived toxins indoxyl sulfate and hippuric acid were previously reported to be associated with altered pharmacokinetics of the immunosuppressant tacrolimus in liver transplant recipients, and ABC transporter proteins are likely to be involved in the transport of such substances, but the role has not been elucidated. The aim of this study was to assess the retention of indoxyl sulfate and hippuric acid in the plasma of liver transplantation subjects carrying different genotypes of and (changes in transporter activity due to genetic variation), and to explore whether genetic variation is involved in altering the relationship between microbe-derived toxins and tacrolimus pharmacokinetics.
Methods: Liver transplantation subjects treated with the immunosuppressive regimen tacrolimus, corticosteroids, and mycophyolate mofetil were included and divided into normal renal function group and chronic kidney disease group.
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