Griseofulvin is anantifungal medication used to treatdermatophytoses (ringworm).[1][2] This includes fungal infections of thenails and scalp, as well as the skin when antifungal creams have not worked.[3] It is taken by mouth.[2]
Griseofulvin is used orally only fordermatophytosis. It is ineffective topically. It is reserved for cases in which topical treatment with creams is ineffective.[8]
Terbinafine given for 2 to 4 weeks is at least as effective as griseofulvin given for 6 to 8 weeks for treatment ofTrichophyton scalp infections. However, griseofulvin is more effective than terbinafine for treatment ofMicrosporum scalp infections.[9][10]
The drug binds totubulin, interfering withmicrotubule function, thus inhibitingmitosis.[11] It binds tokeratin 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 thedermatophyte 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 byP. 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 aClaisen andaldol condensation to form thebenzophenone intermediate. The benzophenone intermediate is thenmethylated viaS-adenosyl methionine (SAM) twice to yield griseophenone C. The griseophenone C is then halogenated at the activated site ortho to thephenol 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.[15] The newly formed grisan skeleton with a spiro center is thenO-methylated by SAM to generate dehydrogriseofulvin. Ultimately, a stereoselective reduction of the olefin on dehydrogriseofulvin byNADPH affords griseofulvin.[16][17]
Griseofulvin is found to alter the bile metabolism ofmice 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.[18]
^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.PMID15520113.S2CID34976866.
^Grove JF, Ismay D, Macmillan J, Mulholland TP, Rogers MA (1951). "The structure of griseofulvin".Chemistry and Industry.11. London: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.Bibcode:1953AJCh....6..360B.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.
