A new griseofulvin derivative from a soft coral-derived fungus Eupenicillium sp. SCSIO41208.

A new griseofulvin derivative, eupenigriseofulvin (1), together with six known compounds, griseofulvin (2), dechlorogriseofluvin (3), dechloroisogriseofulvin (4), trichopyrone (5), 2-(4-hydroxyphenyl)-ethanol (6), and 1-phenylethane-1,2-diol (7), were isolated from the EtOAc extract of Eupenicillium sp. SCSIO41208. The structures of these compounds were elucidated by spectroscopic methods including NMR and mass spectrometry. The absolute configuration of 1 was determined on the basis of electronic circular dichroism (ECD) data analysis.

Chemoselective fluorination and chemoinformatic analysis of griseofulvin: Natural vs fluorinated fungal metabolites.

Griseofulvin is a fungal metabolite and antifungal drug used for the treatment of dermatophytosis in both humans and animals. Recently, griseofulvin and its analogues have attracted renewed attention due to reports of their potential anticancer effects. In this study griseofulvin (1) and related analogues (2-6, with 4 being new to literature) were isolated from Xylaria cubensis. Six fluorinated analogues (7-12) were synthesized, each in a single step using the isolated natural products and Selectflour, so as to examine the effects of fluorine incorporation on the bioactivities of this structural class. The isolated and synthesized compounds were screened for activity against a panel of cancer cell lines (MDA-MB-435, MDA-MB-231, OVCAR3, and Huh7.5.1) and for antifungal activity against Microsporum gypseum. A comparison of the chemical space occupied by the natural and fluorinated analogues was carried out by using principal component analysis, documenting that the isolated and fluorinated analogues occupy complementary regions of chemical space. However, the most active compounds, including two fluorinated derivatives, were centered around the chemical space that was occupied by the parent compound, griseofulvin, suggesting that modifications must preserve certain attributes of griseofulvin to conserve its activity.

Griseofulvin Derivative and Indole Alkaloids from Penicillium griseofulvum CPCC 400528.

A new griseofulvin derivative, 4'-demethoxy-4'-N-isopentylisogriseofulvin (1), three new indole alkaloids, 2-demethylcyclopiamide E (2), 2-demethylsperadine F (3), and clopiamine C (4), and five known metabolites (5-9) were isolated from Penicillium griseofulvum CPCC 400528. Compound 1 is the first reported griseofulvin analogue with an N-isopentane group and the first example of a naturally occurring N-containing griseofulvin analogue. Their structures and absolute configurations were elucidated through extensive spectroscopic analyses, calculated ECD, and single-crystal X-ray diffraction (Cu Kα). The possible biogenetic pathway of 1-3 was proposed. Compounds 1, 2, and 5 exhibited anti-HIV activities with IC50 values of 33.2, 20.5, and 12.6 µM, respectively.

Antimicrobial and allelopathic metabolites produced by Penicillium brasilianum.

Six known compounds, isoroquefortine C (1), griseofulvin (2), ergosterol peroxide (3), 3ß-hydroxy-(22E,24R)-ergosta-5,8,22-trien-7-one (4), cerevisterol (5) and (22E,24R)-6ß-methoxyergosta-7,22-diene-3ß,5α-diol (6), were produced by the fungus Penicillium brasilianum, and their structures were elucidated by spectroscopic methods. This is the first report on isoroquefortine C as naturally occurring compound. Their bioactivities against five phytopathogenic fungi (Gibeberalla saubinetti, Fusarium solani, Botrytis cinerea, Colletotrichum gloeosporioides and Alternaria solani) and four pathogenic bacteria (Escherichia coli, Bacillus subtilis, Staphyloccocus aureus and Bacillus cereus), as well as allelopathic activities on Raphanus sativus were tested. Compound 1 exhibited a remarkable antifungal activity with minimum inhibitory concentration (MIC) of 12.5 µM against C. gloeosporioides, in comparison with positive control hymexazol (MIC 25 µM). Compound 2 displayed strong inhibitory effects on the growth of A. solani and S. aureus with MIC of 3.13 µM for each. Compounds 2 and 3 displayed a significant growth-inhibition activity on R. sativus.

Two new derivatives of griseofulvin from the mangrove endophytic fungus Nigrospora sp. (strain No. 1403) from Kandelia candel (L.) Druce.

Two new compounds, methyl 3-chloro-6-hydroxy-2-(4-hydroxy-2-methoxy-6-methylphenoxy)-4-methoxybenzoate (1) and (2 S,5' R,E)-7-hydroxy-4,6-dimethoxy-2-(1-methoxy-3-oxo-5-methylhex-1-enyl)-benzofuran-3(2H)-one (2), together with four known compounds, griseofulvin (3), dechlorogriseofulvin (4), bostrycin (5), and deoxybostrycin (6), were isolated from the marine endophytic fungus NIGROSPORA sp. (No. 1403) collected from the South China Sea. The structures were elucidated by spectroscopic methods, 1D, 2D NMR, and HREIMS. Compounds 5 and 6 showed moderate antitumor and moderate antimicrobial activity.

Supercritical carbon dioxide extraction of griseofulvin from the solid matrix obtained after solid-state fermentation.

Globally there is an increasing concern to minimize the use of organic solvents, particularly the chlorinated ones because of their suspected human carcinogenicity. The use of ecofriendly carbon dioxide as an alternative to organic solvents would be appropriate in the perspective of green technology. Supercritical carbon dioxide (SC-CO(2)) extraction is suitable for extraction of nonpolar compound with molecular weights less than 400. Griseofulvin is an antifungal antibiotic having a molecular weight of 353, making it amenable to SC-CO(2) extraction. This work brings out the potential of supercritical carbon dioxide extraction (SCFE) for downstream processing of griseofulvin from the solid matrix obtained after solid-state fermentation (SSF). The optimized conditions for SCFE of griseofulvin from dried media after SSF were a flow rate of 0.4 L/min, temperature of 60 degrees C, and contact time of 90 min (30 min static + 60 min dynamic) at a pressure of 450-455 bar.

Detection of griseofulvin in a marine strain of Penicillium waksmanii by ion trap mass spectrometry.

A marine strain of Penicillium waksmanii Zaleski was isolated from a sample of seawater from shellfish-farming area in the Loire estuary (France). The in vitro marine culture showed an important antifungal activity. Bioassay-guided fractionation was used to purify the crude extract. Dereplication by electrospray-ion trap/mass spectrometry (ESI-IT/MS) afforded the identification of the antifungal compound, after a semi-purification consisting of two stages. A comparison of the ionic composition between the active and the non-active fractions allowed the detection of a monocharged ion at m/z 353 containing a chlorine atom, which could be attributed to the antifungal griseofulvin [C17H17ClO6+H]+. Multi-stage fragmentation (MSn) confirmed the identity of the m/z 353 ion of the antifungal fraction as griseofulvin. It is the first description of griseofulvin production by a strain of P. waksmanii and the first chemical study of a strain of this species isolated from marine temperate cold water.

New communesin derivatives from the fungus Penicillium sp. derived from the Mediterranean sponge Axinella verrucosa.

The ethyl acetate extract of Penicillium sp., derived from the Mediterranean sponge Axinella verrucosa, yielded the known compound communesin B (1) and its new congeners communesins C (2) and D (3), as well as the known compounds griseofulvin, dechlorogriseofulvin, and oxaline. All structures were unambiguously established by 1D and 2D NMR and MS data. In several bioassays performed on different leukemia cell lines, the communesins exhibited moderate antiproliferative activity.