Novobiocin

Names

[ CAS No. ]:
303-81-1

[ Name ]:
Novobiocin

[Synonym ]:
Notonesomycin
(3R,4S,5R,6R)-5-Hydroxy-6-[(2-hydroxy-3-{[4-hydroxy-3-(3-methyl-2-buten-1-yl)benzoyl]amino}-8-methyl-4-oxo-4H-chromen-7-yl)oxy]-3-methoxy-2,2-dimethyltetrahydro-2H-pyran-4-yl carbamate (non-preferred name)
Novobiocin

Biological Activity

[Description]:

Novobiocin (Albamycin) is a potent and orally active antibiotic. Novobiocin also is a DNA gyrase inhibitor and a heat shock protein 90 (Hsp90) antagonist. Novobiocin has the potential for the research of highly beta-lactam-resistant pneumococcal infections. Novobiocin shows anti-orthopoxvirus activity[1][2][3][4][6].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> HSP

Research Areas >> Infection

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

Signaling Pathways >> Cell Cycle/DNA Damage >> HSP

Signaling Pathways >> Anti-infection >> Bacterial

[Target]

HSP90

[In Vitro]

Novobiocin (1 mM) competitively inhibits ATP binding to gyrase B to interfere with nucleotide binding and interferes with the association of the co-chaperones Hsc70 and p23 with Hsp90[1]. Novobiocin (200 µM; 24 h) inhibits the rate of repair of both cis-DDP and BCNU induced DNA interstrand cross-links and with a corresponding decrease in the clonogenic survival of the human glioblastoma multiforme cells[2]. Novobiocin (0.3 mM; 48 hours) induces a caspase-3/7 enzyme–dependent apoptosis assays with an induction of approximately three- to fivefold of apoptotic cells in K562, HL60, Mutz-2[5].

[In Vivo]

Novobiocin (25, 50, 100, 200 mg/kg; s.c.; 4 times at 1, 5, 24 and 48 h after infection) shows anti-infection activity in mice infected with amoxicillin-resistant Streptococcus pneumoniae[3]. Animal Model: 30 g adult female Swiss mice (sepsis induced by the penicillin-susceptible strain (AR33118))[3] Dosage: 25, 50, 100, 200 mg/kg Administration: S.c.; given at 1, 5, 24 and 48 h after infection Result: Showed anti-infection activity in mice infected with amoxicillin-resistant S. pneumoniae.

[References]

[1]. Marcu MG, et al. The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone. J Biol Chem. 2000 Nov 24;275(47):37181-6.

[2]. Ali-Osman F, et al. Topoisomerase II inhibition and altered kinetics of formation and repair of nitrosourea and cisplatin-induced DNA interstrand cross-links and cytotoxicity in human glioblastoma cells. Cancer Res. 1993 Dec 1;53(23):5663-8.

[3]. Rodríguez-Cerrato V, et al. Comparative efficacy of novobiocin and amoxicillin in experimental sepsis caused by beta-lactam-susceptible and highly resistant pneumococci. Int J Antimicrob Agents. 2010 Jun;35(6):544-9.

[4]. Eder JP, et al. A phase I clinical trial of novobiocin, a modulator of alkylating agent cytotoxicity. Cancer Res. 1991 Jan 15;51(2):510-3.

[5]. Bhatia S, et al. Targeting HSP90 dimerization via the C terminus is effective in imatinib-resistant CML and lacks the heat shock response.Blood. 2018 Jul 19;132(3):307-320.

[6]. Smee DF. Progress in the discovery of compounds inhibiting orthopoxviruses in animal models. Antivir Chem Chemother. 2008;19(3):115-24.

[7]. Smee DF. Progress in the discovery of compounds inhibiting orthopoxviruses in animal models. Antivir Chem Chemother. 2008;19(3):115-24.

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
848.2±65.0 °C at 760 mmHg

[ Melting Point ]:
170-172°C (lit.)

[ Molecular Formula ]:
C₃₁H₃₆N₂O₁₁

[ Molecular Weight ]:
612.624

[ Flash Point ]:
466.8±34.3 °C

[ Exact Mass ]:
612.231934

[ PSA ]:
200.01000

[ LogP ]:
2.37

[ Vapour Pressure ]:
0.0±3.3 mmHg at 25°C

[ Index of Refraction ]:
1.640

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: CU9080000

CHEMICAL NAME :: Benzamide, N-(7-((3-O-(aminocarbonyl)-6-deoxy-5-C-methyl-4-O-met hyl-beta-L-lyxo- hexopyranosyl)oxy)-4-hydroxy-8-methyl-2-oxo-2H-1-benz opyran-3-yl)-4-hydrox y- 3-(3-methyl-2-butenyl)-

CAS REGISTRY NUMBER :: 303-81-1

LAST UPDATED :: 199410

DATA ITEMS CITED :: 20

MOLECULAR FORMULA :: C31-H36-N2-O11

MOLECULAR WEIGHT :: 612.69

WISWESSER LINE NOTATION :: T66 BOVJ DMVR DQ C2UY1&1& EQ J1 IO- FT6OTJ B1 B1 CV1 DOVZ EQ &-NA-

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Human

DOSE/DURATION :: 171 mg/kg/12D-C

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - conjunctive irritation Skin and Appendages - dermatitis, other (after systemic exposure)

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1500 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 262 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 407 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :: Sister chromatid exchange

TEST SYSTEM :: Rodent - hamster Ovary

DOSE/DURATION :: 200 mg/L

REFERENCE :: CHROAU Chromosoma. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1939- Volume(issue)/page/year: 85,603,1982

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H317

[ Precautionary Statements ]:
P280-P301 + P312 + P330

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport