Nargenicin

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). 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. In murine BV-2 microglial cells, nargenicin (1 µM) inhibits cytokine expression and nitric oxide production induced by LPS. Nargenicin (200 µM), when used in combination with 1,25-dihydroxyvitamin D3 or all-trans retinoic acid (Cay-11017), reduces cell proliferation by 37-47% and increases cell differentiation by 82-85% in HL-60 human myeloid leukemia cells. 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.Formal Name: 1H-pyrrole-2-carboxylic acid, (1E,3R,4S,7S,8aS,10aR,11R,12R,13R,14R,14aS,14bS)-3,4,6,7,8,8a,10a,11,12,13,14,14a-dodecahydro-14-hydroxy-4-[(1R)-1-hydroxyethyl]-7-methoxy-1,3,13-trimethyl-6-oxo-11,14b-epoxy-14bH-naphth[2,1-e]oxecin-12-yl ester. CAS Number: 70695-02-2. Synonyms: Antibiotic 47444, CP 47,444, NSC 355066. Molecular Formula: C28H37NO8. Formula Weight: 515.6. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: soluble, DMSO: soluble, Ethanol: soluble, Methanol: soluble. lambdamax: 267 nm. SMILES: C/C([C@]1(O2)[C@](C[C@@H]3OC)([H])C=C[C@@]4([H])[C@@H]2[C@H](OC(C5=CC=CN5)=O)[C@H](C)[C@@H](O)[C@]41[H])=C\[C@@H](C)[C@]([C@@H](C)O)([H])OC3=O. InChi Code: InChI=1S/C28H37NO8/c1-13-11-14(2)28-17(12-20(34-5)27(33)35-23(13)16(4)30)8-9-18-21(28)22(31)15(3)24(25(18)37-28)36-26(32)19-7-6-10-29-19/h6-11,13,15-18,20-25,29-31H,12H2,1-5H3/b14-11+/t13-,15-,16-,17-,18-,20+,21+,22-,23+,24-,25-,28+/m1/s1. InChi Key: YEUSSARNQQYBKH-SIMZXIQRSA-N. Origin: Bacterium/Nocardia argentinensis.