Macrolides: From Toxins to Therapeutics

Abstract

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.

Ascorbic Acid Ameliorates Cardiac and Hepatic Toxicity Induced by Azithromycin-Etoricoxib Drug Interaction

“…Direct vasodilators target the smooth muscle cells to decrease vascular tone and blood pressure. Azithromycin is in the category of macrolides, which induce phase III-like contractions in the human gastrointestinal tract during the interdigestive state that stimulates motor activity in human smooth muscle receptors [ 24 ]. Azithromycin has also been found to promote gastrointestinal activities and thus there is a direct relationship between the drug interaction and muscular contractions, which may confirm the current findings.…”

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

“…Lobophorolide, however, stabilizes an actin dimer at 2:2 stoichiometry [109]. Although many actin-targeting molecules have been developed and tested for the inhibition of the metastasis of cancer cell lines, none of these molecules were clinically used for their originally designed purpose, presumably because actin is used in normal physiology as well [114]. Nevertheless, these molecules Latrunculin A binds near the actin nucleotide-binding site in a cleft between subdomains 2 and 4 and stabilizes actin monomers (Figure 4), thereby preventing them from repolymerizing into filaments [100].…”

Integrated Analysis of Cecal Microbiome and Metabolome Revealed Different Inflammatory Reponses to Salmonella Enterica Serovar Enteritidis Between Reciprocal Crosses of Chicken

“…For instance, the increase of 5-Formiminotetrahydrofolic acid, a kind of tetrahydrofolic acids which are essential for bacteria growth [22], might be bene cial for or accompanied with Salmonella multiplication. The decrease of 10-Oxo-11-octadecen-13-olide, a kind of macrolides which are generally considered toxic and antibiotic [23], should facilitate Salmonella colonization.…”