Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm).[1] This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked.[2] It is taken by mouth.[1]
Griseofulvin is used orally only for dermatophytosis. It is ineffective topically. It is reserved for cases in which topical treatment with creams is ineffective.[7]
Terbinafine given for 2 to 4 weeks is at least as effective as griseofulvin given for 6 to 8 weeks for treatment of Trichophyton scalp infections. However, griseofulvin is more effective than terbinafine for treatment of Microsporum scalp infections.[8][9]
Pharmacologyedit
Pharmacodynamicsedit
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 binds to fungal microtubules. This alters the processing for mitosis and also underlying information for deposition of fungal cell walls.[citation needed]
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-adenosyl methionine (SAM) 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.[13] 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.[14][15]
Toxicologyedit
Miceedit
Griseofulvin is found to alter the bile metabolism of mice by Yokoo et al. 1979. The same team went on to find a similar effect on mice by a chemically unrelated substance, 3,5-diethoxycarbonyl-1,4-dihydrocollidine, in Yokoo et al. 1982 and Tsunoo et al. 1987.[16]
Referencesedit
^ abcdef"Griseofulvin". The American Society of Health-System Pharmacists. from the original on 20 December 2016. Retrieved 8 December 2016.
^Block SS (2001). Disinfection, Sterilization, and Preservation. Lippincott Williams & Wilkins. p. 631. ISBN9780683307405. from the original on 2016-12-20.
^Ash M, Ash I (2004). Handbook of Preservatives. Synapse Info Resources. p. 406. ISBN978-1-890595-66-1. from the original on 2013-12-31.
^Beekman AM, Barrow RA (2014). "Fungal metabolites as pharmaceuticals". Australian Journal of Chemistry. 67 (6): 827–843. doi:10.1071/ch13639.
^World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 838. ISBN3-8047-1763-2.
^Fleece D, Gaughan JP, Aronoff SC (November 2004). "Griseofulvin versus terbinafine in the treatment of tinea capitis: a meta-analysis of randomized, clinical trials". Pediatrics. 114 (5): 1312–1315. doi:10.1542/peds.2004-0428. PMID 15520113. S2CID 34976866.
^Chen X, Jiang X, Yang M, González U, Lin X, Hua X, et al. (May 2016). "Systemic antifungal therapy for tinea capitis in children". The Cochrane Database of Systematic Reviews. 2016 (5): CD004685. doi:10.1002/14651858.CD004685.pub3. PMC8691867. PMID 27169520.
^Oxford AE, Raistrick H, Simonart P (February 1939). "Studies in the biochemistry of micro-organisms: Griseofulvin, C(17)H(17)O(6)Cl, a metabolic product of Penicillium griseo-fulvum Dierckx". The Biochemical Journal. 33 (2): 240–248. doi:10.1042/bj0330240. PMC1264363. PMID 16746904.
^Grove JF, Ismay D, Macmillan J, Mulholland TP, Rogers MA (1951). "The structure of griseofulvin". Chemistry and Industry. London. 11: 219–220.
^Grove JF, MacMillan J, Mulholland TP, Rogers MA (1952). "762. Griseofulvin. Part IV. Structure". Journal of the Chemical Society (Resumed): 3977. doi:10.1039/JR9520003977.
^Birch A (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 PM (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). UK: John Wiley & Sons Ltd. ISBN978-0-471-97478-9.
^Harris CM, Roberson JS, Harris TM (August 1976). "Biosynthesis of griseofulvin". Journal of the American Chemical Society. 98 (17): 5380–5386. doi:10.1021/ja00433a053. PMID 956563.
^Knasmüller S, Parzefall W, Helma C, Kassie F, Ecker S, Schulte-Hermann R (September 1997). "Toxic effects of griseofulvin: disease models, mechanisms, and risk assessment". Critical Reviews in Toxicology. Taylor & Francis. 27 (5): 495–537. doi:10.3109/10408449709078444. PMID 9347226.
External linksedit
"Griseofulvin". Drug Information Portal. U.S. National Library of Medicine.
griseofulvin, antifungal, medication, used, treat, number, types, dermatophytoses, ringworm, this, includes, fungal, infections, nails, scalp, well, skin, when, antifungal, creams, have, worked, taken, mouth, clinical, datatrade, namesgris, grifulvin, othersah. Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses ringworm 1 This includes fungal infections of the nails and scalp as well as the skin when antifungal creams have not worked 2 It is taken by mouth 1 GriseofulvinClinical dataTrade namesGris peg Grifulvin V othersAHFS Drugs comMonographMedlinePlusa682295PregnancycategoryAU DRoutes ofadministrationBy mouthATC codeD01AA08 WHO D01BA01 WHO Legal statusLegal statusAU S4 Prescription only UK POM Prescription only US onlyPharmacokinetic dataBioavailabilityHighly variable 25 to 70 MetabolismLiver demethylation and glucuronidation Elimination half life9 21 hoursIdentifiersIUPAC name 2S 6 R 7 chloro 2 4 6 trimethoxy 6 methyl 3H 4 H spiro 1 benzofuran 2 1 cyclohex 2 ene 3 4 dioneCAS Number126 07 8 YPubChem CID441140DrugBankDB00400 YChemSpider389934 YUNII32HRV3E3D5KEGGD00209 YChEBICHEBI 27779 YChEMBLChEMBL562 YCompTox Dashboard EPA DTXSID8020674ECHA InfoCard100 004 335Chemical and physical dataFormulaC 17H 17Cl O 6Molar mass352 766 g mol 13D model JSmol Interactive imageSMILES O C2c3c O C 21C OC C C O C C H 1C c Cl c OC cc3OCInChI 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 YKey DDUHZTYCFQRHIY RBHXEPJQSA N Y verify Common side effects include allergic reactions nausea diarrhea headache trouble sleeping and feeling tired 1 It is not recommended in people with liver failure or porphyria 1 Use during or in the months before pregnancy may result in harm to the baby 1 2 Griseofulvin works by interfering with fungal mitosis 1 Griseofulvin was discovered in 1939 from the soil fungus Penicillium griseofulvum 3 4 5 It is on the World Health Organization s List of Essential Medicines 6 Contents 1 Medical uses 2 Pharmacology 2 1 Pharmacodynamics 3 Biosynthesis 4 Toxicology 4 1 Mice 5 References 6 External linksMedical uses editGriseofulvin is used orally only for dermatophytosis It is ineffective topically It is reserved for cases in which topical treatment with creams is ineffective 7 Terbinafine given for 2 to 4 weeks is at least as effective as griseofulvin given for 6 to 8 weeks for treatment of Trichophyton scalp infections However griseofulvin is more effective than terbinafine for treatment of Microsporum scalp infections 8 9 Pharmacology editPharmacodynamics edit 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 binds to fungal microtubules This alters the processing for mitosis and also underlying information for deposition of fungal cell walls citation needed Biosynthesis editIt is produced industrially by fermenting the fungus Penicillium griseofulvum 10 11 12 The first step in the biosynthesis of griseofulvin by P griseofulvin is the synthesis of the 14 carbon poly b 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 b 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 adenosyl methionine SAM 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 13 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 14 15 Toxicology editMice edit Griseofulvin is found to alter the bile metabolism of mice by Yokoo et al 1979 The same team went on to find a similar effect on mice by a chemically unrelated substance 3 5 diethoxycarbonyl 1 4 dihydrocollidine in Yokoo et al 1982 and Tsunoo et al 1987 16 References edit a b c d e f Griseofulvin The American Society of Health System Pharmacists Archived from the original on 20 December 2016 Retrieved 8 December 2016 a b World Health Organization 2009 Stuart MC Kouimtzi M Hill SR eds WHO Model Formulary 2008 World Health Organization p 149 hdl 10665 44053 ISBN 9789241547659 Block SS 2001 Disinfection Sterilization and Preservation Lippincott Williams amp Wilkins p 631 ISBN 9780683307405 Archived from the original on 2016 12 20 Ash M Ash I 2004 Handbook of Preservatives Synapse Info Resources p 406 ISBN 978 1 890595 66 1 Archived from the original on 2013 12 31 Beekman AM Barrow RA 2014 Fungal metabolites as pharmaceuticals Australian Journal of Chemistry 67 6 827 843 doi 10 1071 ch13639 World Health Organization 2019 World Health Organization model list of essential medicines 21st list 2019 Geneva World Health Organization hdl 10665 325771 WHO MVP EMP IAU 2019 06 License CC BY NC SA 3 0 IGO Mutschler E Schafer Korting M 2001 Arzneimittelwirkungen in German 8 ed Stuttgart Wissenschaftliche Verlagsgesellschaft p 838 ISBN 3 8047 1763 2 Fleece D Gaughan JP Aronoff SC November 2004 Griseofulvin versus terbinafine in the treatment of tinea capitis a meta analysis of randomized clinical trials Pediatrics 114 5 1312 1315 doi 10 1542 peds 2004 0428 PMID 15520113 S2CID 34976866 Chen X Jiang X Yang M Gonzalez U Lin X Hua X et al May 2016 Systemic antifungal therapy for tinea capitis in children The Cochrane Database of Systematic Reviews 2016 5 CD004685 doi 10 1002 14651858 CD004685 pub3 PMC 8691867 PMID 27169520 Oxford AE Raistrick H Simonart P February 1939 Studies in the biochemistry of micro organisms Griseofulvin C 17 H 17 O 6 Cl a metabolic product of Penicillium griseo fulvum Dierckx The Biochemical Journal 33 2 240 248 doi 10 1042 bj0330240 PMC 1264363 PMID 16746904 Grove JF Ismay D Macmillan J Mulholland TP Rogers MA 1951 The structure of griseofulvin Chemistry and Industry London 11 219 220 Grove JF MacMillan J Mulholland TP Rogers MA 1952 762 Griseofulvin Part IV Structure Journal of the Chemical Society Resumed 3977 doi 10 1039 JR9520003977 Birch A 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 PM 2009 Medicinal Natural Products A Biosynthetic Approach 3rd ed UK John Wiley amp Sons Ltd ISBN 978 0 471 97478 9 Harris CM Roberson JS Harris TM August 1976 Biosynthesis of griseofulvin Journal of the American Chemical Society 98 17 5380 5386 doi 10 1021 ja00433a053 PMID 956563 Knasmuller S Parzefall W Helma C Kassie F Ecker S Schulte Hermann R September 1997 Toxic effects of griseofulvin disease models mechanisms and risk assessment Critical Reviews in Toxicology Taylor amp Francis 27 5 495 537 doi 10 3109 10408449709078444 PMID 9347226 External links edit Griseofulvin Drug Information Portal U S National Library of Medicine Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Griseofulvin amp oldid 1159423804, wikipedia, wiki, book, books, library,
