Novobiocin

Overview

Novobiocin, also known as albamycin, is an aminocoumarin antibiotic that is produced by the actinomycete Streptomyces niveus, which is a heterotypic synonym for S. spheroides a member of the class Actinomycetia. Other aminocoumarin antibiotics include clorobiocin and coumermycin A1. Novobiocin was first reported in the mid-1950s (then called streptonivicin).[1–4] WP

Pharmacology

Mechanism of action

The molecular basis of action of novobiocin, and other related drugs clorobiocin and coumermycin A1, has been examined. Aminocoumarins are very potent inhibitors of bacterial DNA gyrase and work by targeting the GyrB subunit of the enzyme involved in energy transduction. Novobiocin as well as the other aminocoumarin antibiotics act as competitive inhibitors of the ATPase reaction catalysed by GyrB. The potency of novobiocin is considerably higher than that of the fluoroquinolones that also target DNA gyrase, but at a different site on the enzyme. The GyrA subunit is involved in the DNA nicking and ligation activity.[2][5–8] WP⚠ Wikipedia itself has flagged this text: citation needed.

Novobiocin has been shown to weakly inhibit the C-terminus of the eukaryotic Hsp90 protein (high micromolar IC50). Modification of the novobiocin scaffold has led to more selective Hsp90 inhibitors. Novobiocin has also been shown to bind and activate the Gram-negative lipopolysaccharide transporter LptBFGC.[9][10][11] WP

The ATP binding pocket of polymerase theta is blocked by novobiocin resulting in a loss of ATPase activity. This results in the loss of microhomology-mediated end joining as a pathway for homologous recombination deficient cells to circumvent DNA damaging agents. The action of novobiocin is syngeristic with PARP inhibitors for reducing tumor size in a mouse model.[12] WP

Chemistry

Formula

C31H36N2O11 PC

Molar mass (g/mol)

612.6 PC

IUPAC name (computed by PubChem)

[(3R,4S,5R,6R)-5-hydroxy-6-[2-hydroxy-3-[[4-hydroxy-3-(3-methylbut-2-enyl)benzoyl]amino]-8-methyl-4-oxochromen-7-yl]oxy-3-methoxy-2,2-dimethyloxan-4-yl] carbamate PC

SMILES

CC1=C(C=CC2=C1OC(=C(C2=O)NC(=O)C3=CC(=C(C=C3)O)CC=C(C)C)O)O[C@H]4[C@@H]([C@@H]([C@H](C(O4)(C)C)OC)OC(=O)N)O PC

InChIKey

DYYIUCVAQGRACE-KGSXXDOSSA-N PC

PubChem CID

9346

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Komaki, Hisayuki. Recent progress of reclassification of the genus Streptomyces. Microorganisms. Mar 2023. doi:10.3390/microorganisms11040831 · PMID 37110257 · PMC10145440
2. Other da Silva Eustáquio A. Biosynthesis of aminocoumarin antibiotics in Streptomyces: Generation of structural analogues by genetic engineering and insights into the regulation of antibiotic production. 2004
3. Journal / agency Hoeksema H, Johnson JL, Hinman JW. Structural studies on streptonivicin, a new antibiotic. Journal of the American Chemical Society. December 1955. doi:10.1021/ja01629a129
4. Journal / agency Smith CG, Dietz A, Sokolski WT, Savage GM. Streptonivicin, a new antibiotic. I. Discovery and biologic studies. Antibiotics & Chemotherapy. February 1956. PMID 24543916
5. Journal / agency Maxwell A. The interaction between coumarin drugs and DNA gyrase. Molecular Microbiology. August 1993. doi:10.1111/j.1365-2958.1993.tb01728.x · PMID 8231802
6. Journal / agency Maxwell A. DNA gyrase as a drug target. Biochemical Society Transactions. February 1999. doi:10.1042/bst0270048 · PMID 10093705
7. Journal / agency Lewis RJ, Tsai FT, Wigley DB. Molecular mechanisms of drug inhibition of DNA gyrase. BioEssays. August 1996. doi:10.1002/bies.950180810 · PMID 8760340
8. Journal / agency Maxwell A, Lawson DM. The ATP-binding site of type II topoisomerases as a target for antibacterial drugs. Current Topics in Medicinal Chemistry. 2003. doi:10.2174/1568026033452500 · PMID 12570764
9. Journal / agency Yu XM, Shen G, Neckers L, Blake H, Holzbeierlein J, Cronk B, Blagg BS. Hsp90 inhibitors identified from a library of novobiocin analogues. Journal of the American Chemical Society. September 2005. doi:10.1021/ja0535864 · PMID 16159253
10. Journal / agency Mandler MD, Baidin V, Lee J, Pahil KS, Owens TW, Kahne D. Novobiocin Enhances Polymyxin Activity by Stimulating Lipopolysaccharide Transport. Journal of the American Chemical Society. June 2018. doi:10.1021/jacs.8b02283 · PMID 29746111 · PMC5990483
11. Journal / agency May JM, Owens TW, Mandler MD, Simpson BW, Lazarus MB, Sherman DJ, Davis RM, Okuda S, Massefski W, Ruiz N, Kahne D. The Antibiotic Novobiocin Binds and Activates the ATPase That Powers Lipopolysaccharide Transport. Journal of the American Chemical Society. December 2017. doi:10.1021/jacs.7b07736 · PMID 29135241 · PMC5735422
12. Journal / agency Zhou J, Gelot C, Pantelidou C, Li A, Yücel H, Davis RE, Färkkilä A, Kochupurakkal B, Syed A, Shapiro GI, Tainer JA, Blagg BS, Ceccaldi R, D'Andrea AD. A first-in-class polymerase theta inhibitor selectively targets homologous-recombination-deficient tumors. Nature Cancer. June 2021. doi:10.1038/s43018-021-00203-x · PMID 34179826 · PMC8224818

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.