Nargenicin (Synonyms: Antibiotic 47444)

Nargenicin is a macrolide antibiotic that selectively inhibits the growth of S. aureus, methicilin resistant S. aureus (MRSA), and M. luteus (MICs = 0.6, 0.3, and 2.5 μg/ml, respectively) over a panel of 11 Gram-positive and Gram-negative bacteria (MICs = >80 μg/ml). [1] It dose-dependently inhibits S. aureus DnaE in the presence of DNase I-activated DNA and E. coli DnaE when used at concentrations of 0.00001-0.1 and 0.01-100 μg/mL, respectively. [2] In murine BV-2 microglial cells, nargenicin (1 μM) inhibits cytokine expression and nitric oxide production induced by LPS.[3]  Nargenicin (200 μM), when used in combination with 1,25-dihydroxyvitamin D3 or all-trans retinoic acid , reduces cell proliferation by 37-47% and increases cell differentiation by 82-85% in HL-60 human myeloid leukemia cells.[4]  In vivo, nargenicin (50 mg/kg, p.o.) reduces the number of colony-forming units (CFUs) in infected kidneys by 100,000-fold in a murine model of S. aureus infection.[2]

Reference:
[1]. Sohng, J.K., Yamaguchi, T., Seong, C.N., et al. Production, isolation and biological activity of nargenicin from Nocardia sp. CS682. Arch. Pharm. Res. 31(10), 1339-1345 (2008).
[2]. Painter, R.E., Adam, G.C., Arocho, M., et al. Elucidation of DnaE as the antibacterial target of the natural product, nargenicin. Chem. Biol. 22(10), 1362-1373 (2015).
[3]. Yoo, J.C., Cho, H.S., Park, E., et al. Nargenicin attenuates lipopolysaccharide-induced inflammatory responses in BV-2 cells. Neuroreport 20(11), 1007-1012 (2009).
[4]. Kim, S.H., Yoo, J.C., and Kim, T.S. Nargenicin enhances 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced leukemia cell differentiation via PKCβI/MAPK pathways. Biochem. Pharmacol. 77(11), 1694-1701 (2009).