ИКАРУГАМИЦИН

Ikarugamycin is a macrocyclic antibiotic first isolated from Streptomyces sp. that demonstrates potent antiprotozoal activity. It exhibits cytotoxic effects in cancer cell lines, inhibiting cell proliferation (IC₅₀ = 221.3 nM in HL-60 cells) through genotoxicity and by inducing apoptosis and activation of caspases. It also was shown to significantly inhibit oxidized low-density lipoprotein-induced accumulation of cholesteryl esters in macrophages at 1-4 μM. Additionally, ikarugamycin is used to inhibit clathrin-coated pit-mediated endocytosis.

Ikarugamycin is an unusual pentacyclic tetramic acid produced by Streptomyces phaeochromogenes, with potent activity against the protozoan, Trichomonas vaginalis, reported in 1972. Ikarugamycin also demonstrates selective Gram positive antibacterial activity, and anti-ucler activity possibly via inhibition of H. pylori. 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.

ChEBI: A polyketide macrolactam containing a tetramic acid (2,4-pyrrolidine-2,4-dione) ring system. It is isolated from Streptomyces as an antibitoic with antiprotozoal and cytotoxic activities.