Myrothenones A and B, Cyclopentenone Derivatives with Tyrosinase Inhibitory Activity from the Marine-Derived Fungus Myrothecium sp.

Abstract

New 3-amino-5-ethenylcyclopentenones, myrothenones A (4) and B (5), were isolated together with known 6-n-pentyl-a a-pyrone (1), trichodenone A (2), and cyclonerodiol (3) from the marine algicolous fungus of genus of Myrothecium. The structure and absolute stereochemistry of the new compounds were established by spectral interpretation and X-ray analysis. Compounds 1 and 4 exhibited a tyrosinase inhibitory activity with IC 50 value of 0.8 and 6.6 m mM, respectively, which are more active than kojic acid (IC 50 , 7.7 m mM) currently being used as a functional personal-care compound.Key words marine-derived fungus; Myrothecium sp.; myrothenone; 6-npentyl-a-pyrone; trichodenone A; tyrosinase inhibitory activity Marine microorganisms such as bacteria and fungi inhabit virtually any environment in the sea, and they are the source of greatest diversity in the sea.1,2) The source of increasing interests, these microbes have been shown to produce novel substances with utilities in fine chemicals, drugs and cosmetics, and functional personal-care products. 3)Tyrosinase is known as a key enzyme implicated in the metabolism of melanin in melanocytes, and it is involved in skin-coloring and local hyperpigmentation such as melasma, ephelis, and lentigo. 4)Therefore, the anti-tyrosinase active compounds have been of great concern as functional personal-care products for skin-whitening effects and for preventive and therapeutic effects on the local hyperpigmentation diseases.In our screening aimed at identifying tyrosinase inhibitors of microbial origin, we investigated tyrosinase inhibiting activity from the fungal extracts, and a significant activity was observed in three strains (MFA58, 581 and 898). The anti-tyrosinase active component of two strains (MFA581 and 898) was purified by assay-guided isolation to yield the known kojic acid. 5,6) In a continuing study on the anti-tyrosinase active fungal strain (MFA58), we found 6-n-pentyl-a-pyrone (1), 7) trichodenone A (2), 8) cyclonerodiol (3), 9) and cyclopentenones designated as myrothenones A (4) and B (5) produced by the marine-derived fungus Myrothecium sp. In this paper, the structure determination of 4 and 5 and tyrosinase inhibitory activity of 1 and 4 are reported.The fungal strain (stock #, MFA58) was isolated from the surface of the marine green alga Enteromorpha compressa collected at Baegunpo, Busan in 2002. The fungus, identified to be an Myrothecium sp. by fatty acid methyl ester analysis, 10) was cultured (10 l) in a seawater-based medium.11) The filtered broth was extracted with EtOAc to afford crude extracts (0.8 g). The extract revealed a significant anti-tyrosinase activity, and it was separated by assay-guided fractionation using repeated silica gel flash chromatography (n-hexane in ethyl acetate) and HPLC (ODS-A, MeOH-H 2 Oϭ5 : 1) to yield compounds 1 (150 mg), 2 (3.5 mg), 3 (17.0 mg), 4 (8.0 mg), and 5 (8.5 mg).Myrothenone B (5) 12) was isolated as a colorless oil, which was analyzed for C 7 H 9 NO 2 (4 unsaturations) by HR-FAB-MS and 13 C-NMR methods. ...

Four New Macrocyclic Trichothecenes from Two Strains of Marine-derived Fungi of the Genus Myrothecium

“…Recently, new macrocyclic trichothecenes and other compounds have been isolated from Myrothecium spp. possessing cytotoxic [2ϳ6], antimicrobial [3,7], and tyrosinase inhibitory [8] activities.…”

Bioactive Cyclopentenone Derivatives from Marine Isolates of Fungi

“…The presence of a 1,2,3,3-tetrasubstituted enone chromophore is further supported by the UV spectral data [210 nm (log ε 3.7), 277 (4. . 20 This conclusion is further supported by a comparison of the CD data for myrothenone B (2) and 4. The CD spectrum of 4 is similar to that of myrothenone B (2) and shows a positive Cotton effect at 289 nm (∆ε, +2.9) and a negative Cotton effect at 265 (-1.4), indicating that both compounds share the same configuration at the asymmetric center.…”

“…Therefore, we are interested in their chemical and biological aspect as well as their structureactivity relationships (SARs). As part of an effort to discover biologically active natural products, including cyclopentenones, from marine sources, we investigated the bioactive secondary metabolites of two marine isolates of the fungi, T. viride and R. stolonifer, and isolated three cyclopentenones, 20 myrothenones A (1) and B (2) and trichodenone A (3) from T. viride, isolated from the edible marine red alga, Gracilaria verrucosa, and two cyclopentenones, 21 2-bromomyrothenone B (4) and botrytinone (5), from R. stolonifer, isolated from the edible marine brown alga, Sargassum horneri.…”

Mycochemistry of marine algicolous fungi

“…(−)-Cereoaldomine (353), (−)-cereolactam (354), and conioimide (355) represent unprecedented structural types, which may be yielded by degradation of phenylphenalenone precursors. Among these, myrothenone A (343) significantly inhibited tyrosinase with an IC 50 value of 6.6 μM, which is more potent than kojic acid used currently for personal care (Li et al 2005). Compound 345 showed scavenging activity against DPPH radicals with an IC 50 value of 8.4 μM (Li et al 2006a), and 353-355 selectively inhibited HLE with IC 50 values of 3.01, 9.28, and 0.7 μM, respectively (Elsebai et al 2011b(Elsebai et al , 2012.…”