グリセオフルビン GRF
WordNet
- a kind of penicillin (a fungicidal antibiotic with the trade name Fulvicin) produced by molds of the genus Penicillium (同)Fulvicin
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/18 20:45:12」(JST)
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Griseofulvin
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| Systematic (IUPAC) name |
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(2S,6'R)- 7-chloro- 2',4,6-trimethoxy- 6'-methyl- 3H,4'H-spiro [1-benzofuran- 2,1'-cyclohex[2]ene]- 3,4'-dione
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| Clinical data |
| Trade names |
Gris-peg |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a682295 |
Pregnancy
category |
- B3 (Australia), C (United States)
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| Legal status |
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Routes of
administration |
Oral |
| Pharmacokinetic data |
| Bioavailability |
Highly variable (25 to 70%) |
| Metabolism |
Hepatic demethylation and glucuronidation |
| Biological half-life |
9-21 hours |
| Identifiers |
| CAS Registry Number |
126-07-8 Y |
| ATC code |
D01AA08 D01BA01 |
| PubChem |
CID: 441140 |
| DrugBank |
DB00400 Y |
| ChemSpider |
389934 Y |
| UNII |
32HRV3E3D5 Y |
| KEGG |
D00209 Y |
| ChEBI |
CHEBI:27779 Y |
| ChEMBL |
CHEMBL562 Y |
| Chemical data |
| Formula |
C17H17ClO6 |
| Molecular mass |
352.766 g/mol |
SMILES
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O=C2c3c(O[C@@]21C(/OC)=C\C(=O)C[C@H]1C)c(Cl)c(OC)cc3OC
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InChI
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InChI=1S/C17H17ClO6/c1-8-5-9(19)6-12(23-4)17(8)16(20)13-10(21-2)7-11(22-3)14(18)15(13)24-17/h6-8H,5H2,1-4H3/t8-,17+/m1/s1 Y
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Key:DDUHZTYCFQRHIY-RBHXEPJQSA-N Y
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| Y (what is this?) (verify) |
Griseofulvin (marketed under the proprietary name Grifulvin V by Orthoneutrogena Labs, according to FDA orange book) is an orally administered antifungal drug. It is used both in animals and humans, to treat fungal infections of the skin (commonly known as ringworm) and nails. It is produced by culture of some strains of the mold Penicillium griseofulvum, from which it was isolated in 1939.[1][2]
It is an antibiotic produced by the mycelial fungus Penicillium patulum.[3][4][5][6][7][8][9][10]
It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[11]
Biosynthetic pathway of griseofulvin
Contents
- 1 Biosynthetic process
- 2 Medical uses
- 3 Side effects
- 4 Common brand names
- 5 Mechanism
- 6 References
- 7 External links
Biosynthetic process
The first step in the biosynthesis of griseofulvin by P. griseofulvin is the synthesis of the 14-carbon poly-β -keto chain by a type I iterative polyketide synthase (PKS) via iterative addition of 6 malonyl-CoA to an acyl-CoA starter unit. The 14-carbon poly-β -keto chain undergoes cyclization/aromatization, using cyclase/aromatase, respectively, through a Claisen and aldol condensation to form the benzophenone intermediate. The benzophenone intermediate is then methylated via S-adenosylmethionine twice to yield griseophenone C. The griseophenone C is then halogenated at the activated site ortho to the phenol group on the left aromatic ring to form griseophenone B. The halogenated species then undergoes a single phenolic oxidation in both rings forming the two oxygen diradical species. The right oxygen radical shifts alpha to the carbonyl via resonance allowing for a stereospecific radical coupling by the oxygen radical on the left ring forming a tetrahydrofuranone species . [12] The newly formed grisan skeleton with a spiro center is then O-methylated by SAM to generate dehydrogriseofulvin. Ultimately, a stereoselective reduction of the olefin on dehydrogriseofulvin by NADPH affords griseofulvin. [13][14]
Medical uses
Griseofulvin is used orally only for dermatophytosis. It is ineffective topically. It is reserved for cases with nail, hair, or large body surface involvement.[15]
Side effects
Known side effects of griseofulvin include:
- Can reduce the effectiveness of oral contraceptives as it is a cytochrome p450 enzyme inducer
- Confusion
- Considered unsafe for those with porphyria
- Diarrhea
- Dizziness
- Fatigue
- Headache
- Urticaria
- Impairment of performance of routine activities
- Impairment of liver enzymatic activity
- Inability to fall or stay asleep
- Itching
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- Loss of taste sensation
- Nausea
- Oral thrush (yeast infection of the mouth)
- Possibly a teratogen inducing mutations
- Sensitivity to alcohol, with a disulfiram- (Antabuse)-like reaction
- Sensitivity to prolonged sun exposure
- Skin rashes (including Steven-Johnson syndrome)
- Swelling
- Tingling in the hands or feet
- Upper abdominal pain
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Common brand names
- Grifulvin V
- Gris-PEG
- S-Fulvin
- Crivicin
- Grison-250 (V.I.P Pharma)
- Grisovin-FP (GSK)
- Gris OD 375 (DR.REDDY'S)
Mechanism
The drug binds to tubulin, interfering with microtubule function, thus inhibiting mitosis. It binds to keratin in keratin precursor cells and makes them resistant to fungal infections. The drug reaches its site of action only when hair or skin is replaced by the keratin-griseofulvin complex. Griseofulvin then enters the dermatophyte through energy-dependent transport processes and bind to fungal microtubules. This alters the processing for mitosis and also underlying information for deposition of fungal cell walls.
References
- ^ Michael Ash; Irene Ash (2004). Handbook of Preservatives. Synapse Info Resources. p. 406. ISBN 978-1-890595-66-1.
- ^ Goldman, Leon (6 February 1960). "Current status of Griseofulvin". Journal of the American Medical Association 172 (6): 532. doi:10.1001/jama.1960.03020060022006.
- ^ GB 784618
- ^ U.S. Patent 2,900,304
- ^ U.S. Patent 3,038,839
- ^ U.S. Patent 3,069,328
- ^ U.S. Patent 3,069,329
- ^ http://www.biochemj.org/bj/033/bj0330240.htm
- ^ J.F. Grove, D. Ismay, J. Macmillan, T.P.C. Mulholland, M.A.T. Rogers, Chem. Ind. (London), 219 (1951).
- ^ Grove, J. F.; MacMillan, J.; Mulholland, T. P. C.; Rogers, M. A. T. (1952). "762. Griseofulvin. Part IV. Structure". Journal of the Chemical Society (Resumed): 3977. doi:10.1039/JR9520003977. edit
- ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ Birch, Arthur (1953). "Studies in relation to biosynthesis I. Some possible routes to derivatives of orcinol and phloroglucinol". Australian Journal of Chemistry 6 (4): 360. doi:10.1071/ch9530360.
- ^ Dewick, Paul M. (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). UK: John Wiley & Sons Ltd. ISBN 0-471-97478-1.
- ^ Harris, Constance (1976). "Biosynthesis of Griseofulvin". Journal of the American Chemical Society 98 (17): 5380–5386. doi:10.1021/ja00433a053.
- ^ Tripathi. Textbook of Pharmacology. Jaypee Brothers. pp. 761–762. ISBN 81-8448-085-7.
External links
- Griseofulvin (Medline Plus)
- Antifungal drug causes preferential apoptosis of cancer cells (Oncolink Cancer News)
- Anti-fungal Drug May Help Treat Cancer, Say Scientists at UC Santa Barbara
- dermnetnz Mentions alcohol, contraceptive interactions
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Antifungals (D01 and J02)
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Wall/
membrane |
Ergosterol
inhibitors |
Azoles
(lanosterol 14
alpha-demethylase inhibitors) |
| Imidazoles |
- Topical: bifonazole
- butoconazole
- chlormidazole
- clotrimazole#
- croconazole
- econazole
- fenticonazole
- ketoconazole
- isoconazole
- miconazole#
- neticonazole
- omoconazole
- oxiconazole
- sertaconazole
- sulconazole
- tioconazole
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| Triazoles |
- Topical: (fluconazole#, fosfluconazole
- terconazole)
- Systemic: (fluconazole
- hexaconazole
- isavuconazole
- itraconazole
- posaconazole
- voriconazole)
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| Thiazoles |
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Polyene antimycotics
(ergosterol binding) |
- Topical: (hamycin
- natamycin
- nystatin#)
Systemic: (amphotericin B#, hamycin)
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Allylamines
(squalene monooxygenase
inhibitors) |
- Topical: (amorolfine
- butenafine
- naftifine
- terbinafine)
Systemic: terbinafine
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β-glucan synthase
inhibitors |
- echinocandins (anidulafungin
- caspofungin
- micafungin)
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| Intracellular |
Pyrimidine analogues/
thymidylate synthase inhibitors |
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| Mitotic inhibitors |
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| Aminoacyl tRNA synthetase inhibitors |
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| Others |
- bromochlorosalicylanilide
- methylrosaniline
- tribromometacresol
- undecylenic acid
- polynoxylin
- chlorophetanol
- chlorphenesin
- ticlatone
- sulbentine
- ethylparaben
- haloprogin
- salicylic acid
- selenium disulfide#
- ciclopirox
- amorolfine
- dimazole
- tolnaftate
- tolciclate
- sodium thiosulfate#
- Whitfield's ointment#
- potassium iodide#
- taurolidine
- tea tree oil
- citronella oil
- lemon grass
- orange oil
- patchouli
- lemon myrtle
- PCP: pentamidine
- dapsone
- atovaquone
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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Index of fungal disease
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| Description |
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| Disease |
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| Treatment |
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UpToDate Contents
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English Journal
- Metabolite profiling using liquid chromatography/quadrupole time-of-flight mass spectrometry for the identification of a suitable marker and target matrix of griseofulvin use in bovines.
- Tarbin JA, Fussell RJ.SourceFood and Environment Research Agency, York, YO41 1LZ, UK.
- Rapid communications in mass spectrometry : RCM.Rapid Commun Mass Spectrom.2013 Jun 30;27(12):1287-93. doi: 10.1002/rcm.6574.
- RATIONALE: Griseofulvin is an antifungal agent with potential for misuse in food-producing animals. Little is known about its metabolism in ruminants and hence what are suitable marker residues and target matrices for monitoring purposes.METHODS: Tissues harvested from cattle treated with the antifu
- PMID 23681805
- Development and validation of a reversed phase liquid chromatographic method for analysis of griseofulvin and impurities.
- Kahsay G, Adegoke AO, Van Schepdael A, Adams E.SourceLaboratorium voor Farmaceutische Analyse, Faculteit Farmaceutische Wetenschappen, KU Leuven, O&N2, PB-923, Herestraat 49, B-3000 Leuven, Belgium.
- Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2013 Jun;80:9-17. doi: 10.1016/j.jpba.2013.02.035. Epub 2013 Mar 4.
- A simple and robust reversed phase liquid chromatographic method was developed and validated for the quantitative determination of griseofulvin (GF) and its impurities in drug substances and drug products (tablets). Chromatographic separation was achieved on a Discovery C18 (250mm×4.6mm, 5μm) colu
- PMID 23518305
Japanese Journal
- The Effect of Wellsolve, a Novel Solubilizing Agent, on the Intestinal Barrier Function and Intestinal Absorption of Griseofulvin in Rats
- Hamid Khuriah Abdul,Lin Yulian,Gao Yang,Katsumi Hidemasa,Sakane Toshiyasu,Yamamoto Akira
- Biological & Pharmaceutical Bulletin 32(11), 1898-1905, 2009
- … The model drugs used in this study were 5(6)-carboxyfluorescein (CF), rhodamine123 (a P-glycoprotein substrate), cephalexin (a typical substrate for PEPT1) and griseofulvin (a BCS Class II drug). … Furthermore, intestinal absorption of griseofulvin in the presence of 10% (v/v) Wellsolve significantly increased as compared with the control. …
- NAID 130000116965
- Manifestation of psychiatric behaviors in a mouse model of griseofulvin-induced hepatic porphyria
- Satoh Yoko,Iwadate Reiko,Watanabe Yukino,Kawai Hiroshi,Kudo Naomi,Kawashima Yoichi,Mitsumoto Atsushi
- Journal of toxicological sciences 33(5), 599-608, 2008-12-01
- … In the present study, we observed psychiatric behaviors in mice with hepatic porphyria induced by the ingestion of a griseofulvin (GF)-containing diet over a period of 12 weeks. …
- NAID 110007005559
Related Links
- Griseofulvin (marketed under the proprietary name Grifulvin V by Orthoneutrogena Labs, according to FDA orange book) is an antifungal drug that is administered orally. It is used both in animals and in humans, to treat fungal infections of the ...
- Griseofulvin comes as a tablet, capsule, and liquid to take by mouth. It is usually taken once a day or can be taken two to four times a day. Although your symptoms may get better in a few days, you will have to take griseofulvin for a long time ...
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