Ikarugamycin is a natural product with an unusual structure, a pentacyclic tetramic acid produced by Streptomyces phaeochromogenes. Discovered in 1972, the compound belongs to the polycyclic tetramate macrolactams (PTMs) class. It has potent activity against the protozoan, Trichomonas vaginalis. It also demonstrates selective Gram-positive antibacterial activity. In addition, Ikarugamycin inhibits the uptake of oxidized low-density lipoprotein in mouse macrophages, blocks PMA and Nef-mediated cell surface CD4 down-regulation, and inhibits clathrin-coated pit-mediated endocytosis. Importantly, Ikarugamycin is emerging as a useful agent for studying the process of endocytosis.
Ikarugamycin is soluble in ethanol, methanol, DMF or DMSO. Limited water solubility.
| Molecular Formula | C29H38N2O4 |
| Source | Streptomyces phaeochromogenes |
| Spectrum | Ikarugamycin has Gram-positive antibacterial activity and specific anti-protozoal activity. |
| Eukaryotic cell culture applications |
Ikarugamycin was explored in an in vitro infection model with bovine mammary cell lines to study persistent bovine mastitis caused by intracellular Staphylococcus aureus and was found to kill S. aureus within the mammary epithelial cell (Saeed et al, 2021). This research is important because the intracellular survival of S. aureus within bovine udder cells has rendered many antibiotics ineffective. Minimum inhibitory concentration (MIC) was used to determine the antibacterial activity of Ikarugamycin, and Mac-T cells were infected with S. aureus using the gentamicin protection assay. The antibiotic killed 90% of intracellular S. aureus at 5 μg/mL concentration. Ikarugamycin inhibits the accumulation of lipid droplets and cholesterol ester in the macrophage (Hasumi et al, 1992). Ikarugamycin has also been used as an inhibitor for the clathrin-mediated endocytosis uptake pathway in mammalian cells. |
| References |
Elkin SR et al (2016) Ikarugamycin: A natural product inhibitor of clathrin-mediated endocytosis. Traffic. 17(10):1139-1149 Hasumi K, Shinohara C, Naganuma S and Endo A (1992) Inhibition of the uptake of oxidized low-density lipoprotein in macrophage J774 by the antibiotic Ikarugamycin. Eur. J. Biochem. 205(2):841-846 Jomom K, Kuroda Y, Ajisaka M and Sakai H (1972) A new antibiotic, Ikarugamycin. J. Antibiot. 25:271-280 Luo et al (2001) Human immunodeficiency virus type 1 Nef-induced CD4 cell surface downregulation is inhibited by Ikarugamycin. J. Virol. 75:2488 Saeed SI et al (2021) Antibacterial activity of Ikarugamycin against intracellular Staphylococcus aureus in bovine mammary epithelial cells in vitro infection model. Biology. 10(10):958 |