New isoindolinone derivatives isolated from the fruiting bodies of the basidiomycete Hericium coralloides

doi:10.21203/rs.3.rs-3598064/v1

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New isoindolinone derivatives isolated from the fruiting bodies of the basidiomycete Hericium coralloides

https://doi.org/10.21203/rs.3.rs-3598064/v1

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published 22 Dec, 2023

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Preparative high performance liquid chromatography (HPLC) purification of the ethyl acetate extracts derived from dried basidiomes of the European mushroom Hericium coralloides led to the identification of two previously undescribed isoindolinone derivatives named corallocins D and E (1–2). The structures of the compounds were elucidated based on HR-ESIMS (high-resolution electron spray ionization mass spectroscopy), interpretation of 1D and 2D NMR spectra, circular dichroism (CD) experiments, and comparisons with published and theoretical data. The metabolites were tested for their cytotoxic and antimicrobial effects in vitro where weak to moderate biological effects were observed against HeLa cells (KB 3.1), Mucor hiemalis and Bacillus subtilis.

Hericium

corallocins

antimicrobial

antiproliferative

Basidiomycota fungi, well-known for their profuse production of bioactive molecules thus come in handy (Sandargo et al. 2019). In particular, fungal meroterpenoids have displayed various bioactivities and structural diversities (Geris and Simpson 2009; Jiang et al. 2021). This class of terpenoids, majorly produced via the mixed terpene biosynthetic pathways, is found ubiquitously in animals, plants, Actinobacteria and fungi (Jiang et al. 2021). Among the potent meroterpenoid drugs are; mycophenolic acid and its derivative (mycophenolate mofetil), used as an immunosuppressive drug in organ transplant and cancer chemotherapy (Benjanuwattra et al. 2020).

Mushrooms belonging to the genus Hericium, especially H. erinaceus (lion’s mane) are majorly cultivated as foods, and remain a valuable reservoir of meroterpenoids (Thongbai et al. 2015). According to a recent review, Hericium mushrooms global export and import market values were USD 963.4 million and USD 978.83 million in 2021, respectively (Niego et al., 2023). Meroterpenoids have been widely reported from various species of the fungal genus for their neuroprotective effects (Wang et al. 2015; Wittstein et al. 2016; Ryu et al. 2021; Sum et al., 2023). Nonetheless, Hericium meroterpenes have also been reported for other health-promoting capabilities such as their antidiabetic, antimicrobial, anticancer, immunomodulatory, and hypolipidemic effects (Thongbai et al. 2015).

Thus, as part of our ongoing search of novel antimicrobials from fungi belonging to the phylum Basidiomycota, we discovered two hitherto unprecedented isoindolinone-type meroterpenoids from H. coralloides. Their chemical analyses and bioassays are herein described.

General experimental procedures

HPLC-DAD/MS analyses were performed on the amaZon speed ETD ion trap mass spectrometer (Bruker Daltonics, Bremen, Germany) in the positive and negative ionization modes simultaneously. The HPLC system [C₁₈ Acquity UPLC BEH (Waters) column (stationary phase) and solvent A (H₂O + 0.1% formic acid) + solvent B (ACN + 0.1% formic acid) (solvent system)], was used. The elution gradient applied was an initial 5% B for 0.5 min, followed by an increase to 100% B in 20 min. Thereafter, an isocratic condition was maintained at 100% B for 10 min. The flow rate was 0.6 mL/min and the UV/Vis detections were recorded at 190–600 nm and 210 nm.

HR-ESIMS (high-resolution electrospray ionization mass spectrometry) analyses were measured on the MaXis ESI-TOF (Time of Flight) mass spectrometer (Bruker Daltonics) coupled to an Agilent 1260 series HPLC-UV system (Agilent Technologies, Santa Clara, CA, USA). The HPLC system [C18 Acquity UPLC BEH (ultraperformance liquid chromatography) (ethylene bridged hybrid) (Waters) column (stationary phase) and solvent A (H₂O + 0.1% formic acid) + solvent B (ACN + 0.1% formic acid) (solvent system)], was used. The separation gradient employed was an initial 5% B for 0.5 min, followed by an increase to 100% B in 19.5 min. Subsequently, the gradient was held at isocratic conditions at 100% B for 5 min. The flow rate was maintained at 0.6 mL/min (40°C) and the UV/Vis detection at 200–600 nm. Compass DataAnalysis 4.4 SR1 software was used to determine the molecular formulas of the compounds using the Smart Formula algorithm (Bruker Daltonics).

The NMR spectra were recorded on Avance III 500 (Bruker, Bremen, Germany) (¹H: 500 MHz, ¹³C: 125 MHz) spectrometer locked to the respective deuterium signal of the solvent. Deuterated DMSO-d₆ was used as a solvent in the NMR measurements, where chemical shifts were determined in parts per million (ppm) and coupling constants in Hertz (Hz). Optical rotation was measured in dimethylsulfoxide (Uvasol, Merck, Darmstadt, Germany) solvent using Anton Paar MCP-150 Polarimeter (Graz, Austria) with sodium D line at 589 nm and 100 mm path length. The UV spectra were recorded on the Shimadzu UV/Vis 2450 spectrophotometer (Kyoto, Japan), and ECD (electronic circular dichroism) spectra were measured on the J-815 spectropolarimeter (Jasco, Pfungstadt, Germany) in dimethylsulfoxide solvent (Uvasol).

Chemicals and solvents (analytical and HPLC grade) used were obtained from AppliChem GmbH (Darmstadt, Germany), Avantor Performance Materials (Deventer, Netherlands), Merck KGaA (Darmstadt, Germany) and Carl Roth GmbH & Co. KG (Karlsruhe, Germany).

Fungal Material

The dried fruiting bodies of H. coralloides used in this study were obtained from KÄÄPÄ Biotech, Finland, where they had been grown articficially.

Extraction of metabolites

The dried basidiomes were ground in a mortar to yield a powdered sample (9 g). The powder was soaked with acetone (200 mL), and placed on a shaker (120 rpm), at 25°C for 48 hr. The sample was thereafter filtered and the residue was extracted twice with acetone (200 mL). The filtrate obtained was then dried on reduced pressure using a rotary evaporator and extracted with ethyl acetate as previously described (Wittstein et al. 2016). This yielded 272 mg of ethyl acetate crude extract.

Isolation of compounds 1 and 2

The total extract obtained above (272 mg) was purified using the preparative reverse-phase liquid chromatography system (PLC 2020; Gilson, Middleton, WI, USA) equipped with C₁₈ VP-Nucleodur column 100 − 5 (250 mm × 40 mm, 7 µm, Machery-Nagel, Düren, Germany), while using deionized water + 0.1% formic acid (solvent A) and acetonitrile (MeCN) + 0.1% formic acid (solvent B), as a solvent system. The applied gradient to elute the metabolites was as follows: initial holding at 5% B for 10 min, 5–45% solvent B (50 min), 45–90% B (5 min), 90–100% B (5 min) and isocratic conditions at 100% solvent B (20 min), to yield 1 (1.0 mg; t_R = 74 min) and 2 (0.7 mg; t_R = 76 min). The flow rate was maintained at 40 mL/min, and the UV detections were made at 190, 210 and 280 nm.

Corallocin D (1): Brown amorphous solid; \({\text{[α]}}_{\text{D}}^{\text{20}}\)+24 (c 0.1, DMSO); UV/Vis (DMSO): λ_max (log ε) 257.5 (0.9); NMR data (¹H: 500 MHz, ¹³C: 125 MHz, DMSO-d₆) see Table 1; HR-ESIMS: m/z 388.2123 [M + H]⁺ (calcd. 388.2118 for C₂₂H₃₀NO₅⁺), m/z 410.1946 [M + Na]⁺ (calcd. 410.1938 for C₂₂H₂₉NaNO₅⁺), m/z 775.4183 [2M + H]⁺ (calcd. 775.4164 for C₄₄H₅₉N₂O₁₀⁺), m/z 797.4001 [2M + Na]⁺ (calcd. 797.3984 for C₄₄H₅₈NaN₂O₁₀⁺).

Corallocin E (2): Brown amorphous solid; \({\text{[α]}}_{\text{D}}^{\text{20}}\)+26 (c 0.1, DMSO); UV/Vis (DMSO): λ_max (log ε) 220 (0.5); NMR data (¹H: 500 MHz, ¹³C: 125 MHz, DMSO-d₆) see Table 1; HR-ESIMS: m/z 464.2438 [M + H]⁺ (calcd. 464.2431 for C₂₈H₃₄NO₅⁺), m/z 486.2258 [M + Na]⁺ (calcd. 486.2251 for C₂₈H₃₃NaNO₅⁺), m/z 927.4806 [2M + H]⁺ (calcd. 927.4790 for C₅₆H₆₇N₂O₁₀⁺), m/z 949.4625 [2M + Na]⁺ (calcd. 949.4610 for C₅₆H₆₆NaN₂O₁₀⁺).

Antimicrobial assay

Minimum inhibitory concentrations (MICs) were determined via serial dilutions on 96-well microtiter plates against various test microorganisms as previously established (Sum et al., 2022). YMG (yeast-malt-glucose) medium was used in the growth of filamentous fungi and yeasts, whereas EBS medium (0.5% casein peptone, 0.1% meat extract, 0.1% yeast extract, 0.5% glucose, 50 mM HEPES [11.9 g/L] and pH = 7.0) was used for the growth of bacteria. The test strains included bacteria: Staphylococcus aureus [DSM 346], Bacillus subtilis [DSM 10], Acinetobacter baumanii [DSM 30008], Escherichia coli [DSM 1116], Chromobacterium violaceum [DSM 30191], Pseudomonas aeruginosa [PA14] and Mycolicibacterium smegmatis [ATCC 700084]); and fungi: Candida albicans [DSM 1665], Mucor hiemalis [DSM 2656], Schizosaccharomyces pombe [DSM 70572], Rhodotorula glutinis [DSM 10134], and Pichia anomala [DSM 6766]. Ciprofloxacin, kanamycin, gentamycin, and oxytetracycline were used as positive controls against bacteria, whereas nystatin was used against fungi. The lowest concentration, at which no growth of the test organism was observed, was determined as the MIC.

Cytotoxicity assay

Mammalian cell lines obtained from the DSMZ collection (Braunschweig, Germany), including mouse fibroblasts (L929), human endocervical adenocarcinoma (KB3.1), epidermoid carcinoma (A431), ovarian cancer (SKOV-3), prostate cancer (PC3), breast cancer (MCF-7) and human lung adenocarcinoma (A549) cell lines, were used in the determination of in vitro cytotoxicity (IC₅₀) of compounds 1–2. MC-7, SKOV-3 and A431 were cultured in RPMI (Gibco), A549, KB 3.1 and L929 in DMEM (Gibco) and PC-3 in F12-K (Gibco). The cells (supplemented with 10% Gibco bovine serum, were initially grown at 37°C for 5 days under 10% carbon dioxide (CO₂). Thereafter, cytotoxicity of the compounds was determined using the MTT (3-(4,5-dimethylthiazol-2- yl)-2, 5 diphenyltetrazolium bromide) in 96-well microplates in accordance with our standard protocols (Sum et al. 2022). Epothilone B was used as the positive control.

Computational functional theory calculations

A conformational analysis was performed to reveal all possible conformations of compound 1 within 10 kcal/mol energy window with the aid of Omega2 software version 2.5.1.4 (2017). The generated conformations were then geometrically optimized at the B3LYP/6-31G* level of theory. On the optimized structures, frequency computations were performed, and Gibbs free energies were subsequently evaluated. Utilizing the polarizable continuum model (PCM), the initial fifty excitation states were obtained by employing time-dependent density functional theory (TDDFT)-ECD computations in the presence of DMSO. The ECD spectra were extracted and subjected to Boltzmann averaging using SpecDis 1.71 software (Bruhn et al, 2013; Bruhn, 2017). The Boltzmann-weighted curve was then compared to the experimental spectra. Gaussian09 software was utilized to perform all the executed quantum computations (Frisch et al. 2009).

HPLC-DAD/MS investigation of the EtOAc extract derived from the fruiting bodies of H. coralloides revealed two previously undescribed isoindolinone derivatives (1 and 2 in Fig. 1), albeit in very low amounts. The compounds were isolated and subjected to antimicrobial and cytotoxicity assays. In this study, we report the identification and structure elucidation of 1 and 2, as well as their bioassay results.

Compound 1 was isolated as a brown amorphous solid. Its molecular formula was determined to be C₂₂H₂₉NO₅ based on HRESIMS that revealed two peaks for a protonated molecule and a sodium adduct at m/z 388.2123 [M + H]⁺ and at m/z 410.1946 [M + Na]⁺ calculated for 388.2118 and 410.1938, respectively. The determined molecular formula indicated nine degrees of unsaturation. The ¹³C NMR spectrum of 1 (Table 1, Figure S4) revealed the presence of twenty-two carbon resonances distinguished into nine quaternary carbons including two carbonyl carbons at δ_C 174.1 and δ_C 167.7 together with seven aromatic carbon atoms (δ_C 158.2, δ_C 150.5, δ_C 133.8, δ_C 131.6, δ_C 130.6, δ_C 121.4, δ_C 119.6). In addition, the ¹³C NMR data of 1, also revealed four tertiary carbon atoms differentiated into three olefinic (δ_C 124.2, δ_C 122.6, δ_C 95.9) and one aliphatic (δ_C 50.5), alongside with four secondary carbon atoms (δ_C 44.9, δ_C 39.4, δ_C 26.2, δ_C 22.4) and five primary carbon atoms including one interpreted as a methoxy group (δ_C 55.8) and four other methyl groups (δ_C 25.5, δ_C 17.6, δ_C 16.7, δ_C 16.0).

The ¹H NMR, ¹H-¹H COSY and HSQC spectra of 1 (Table 1, Fig. 2, Figures S3, S5, S7), revealed a geranyl side chain presumably biosynthesized through head-to-tail addition of active dimethylallyl and isopentenyl moieties supported by the presence of two olefinic protons at δ_H 5.11 (td, J = 7.2, 1.3 Hz) and at δ_H 5.02 (ddt, J = 7.0, 3.1, 1.3 Hz), which exhibited long-range correlation in ¹H-¹H COSY spectrum to olefinic methyl groups at δ_H 1.72 (d, J = 1.3 Hz), δ_H 1.59 (d, J = 1.3 Hz) and δ_H 1.52 (d, J = 1.3 Hz), respectively, together with three methylene groups at δ_H 3.30 (d, J = 7.2 Hz), δ_H 1.98 (q, J = 7.4 Hz) and δ_H 1.88 (t, J = 7.0 Hz). In addition, the ¹H NMR spectrum of 1 showed an aromatic singlet proton at δ_H 6.70 and two diastereotopic protons at δ_H 4.25 and δ_H 4.54 with a common geminal coupling constant (J-value) of 17.3 Hz. A literature search of 1 indicated that it is probably a previously undescribed isoindolinone derivative related to hericerin, corallocins B and C that were previously described from the fruiting bodies of Hericium erinaceus (Kimura et al. 1991, as “erinaceum”) and H. coralloides (Wittstein et al. 2016), respectively. A detailed comparison of ¹H and ¹³C NMR data of 1 to those reported in literature (Kimura et al. 1991; Wittstein et al. 2016), obviously revealed that 1 comprises a methyl doublet at δ_H 1.38 (d, J = 7.4 Hz; δ_C 16.7) that was correlated by ¹H-¹H COSY spectrum and HMBC spectrum (Fig. 2) to an oxygenated aliphatic methine proton at δ_H 4.63 (q, J = 7.4 Hz; δ_C 50.5) and a carbonyl carbon at δ_C 174.1, respectively, indicating the presence of 3-hydroxybutyryl moiety. Further confirmation to the depicted structure of 1 (Fig. 1) as an isoindolinone derivative was provided by HMBC spectrum (Fig. 2) that disclosed key correlations from a methoxy group at δ_H 3.78 (OCH₃-8), a methylene group at δ_H 3.30 (d, J = 7.2 Hz, H₂-1') and an aromatic proton at δ_H 6.70 (H-7) to an oxygenated aromatic carbon at δ_C 158.2 (C-6) indicating the positions of geranyl side chain, methoxy group and aromatic proton to be on three adjacent carbons (C5-C7), respectively.

The location of 3-hydroxybutyryl moiety was confirmed by ROESY spectrum (Fig. 2) that revealed a key ROE correlation from a methyl doublet at δ_H 1.38 (d, J = 7.4 Hz, H₃-3'') to a diastereotopic methylene group at δ_H 4.25/δ_H 4.54 (H₂-3) indicating the 3-hydroxybutyryl moiety to be located at nitrogen atom of the isoindolinone structure (N-2). The absolute configuration of C-2'' was unambiguously determined by comparing the measured and the calculated ECD spectrum (Fig. 3). This comparsion unveiled a close resemblance between the measured ECD spectrum of 1 and that calculated for (2''R) while revealed an opposite pattern to the calculated ECD spectrum of its enantiomer. Hence, the absolute configruatoin of 1 was unambiguously confirmed to be (2''R). Based on the obtained results, compound 1 was identified as a previously undescribed isoindolinone derivative that was given a trivial name, corallocin D.

Table 1

1D (¹H and ¹³C) NMR data of 1 and 2.
Pos.	1		2
Pos.	δ_C,^a,c type	δ_H^b (multi., J in Hz)	δ_C,^a,c type	δ_H^b (multi., J in Hz)
1	167.7, CO		168.1, CO
3	44.9, CH₂	α 4.25 (d, 17.3, 1H) β 4.54 (d, 17.3, 1H)	45.3, CH₂	α 4.22 (d, 17.0, 1H) β 4.33 (d, 17.0, 1H)
3a	121.4, C		121.2, C
4	150.5, C		149.9, C
5	119.6, C		120.3, C
6	158.2, C		158.3, C
7	95.9, CH	6.70 (s, 1H)	96.5, CH	6.68 (s, 1H)
7a	131.6, C		130.7, C
8	55.8, CH₃	3.78 (s, 3H)	55.8, CH₃	3.76 (s, 3H)
1'	22.4, CH₂	3.30 (d, 7.2, 2H)	22.3, CH₂	3.29 (d, 7.2, 2H)
2'	122.6, CH	5.11 (td, 7.2, 1.3, 1H)	122.2, CH	5.09 (td, 7.2, 1.4, 1H)
3'	133.8, C		134.1, C
4'	39.4, CH₂	1.88 (t, 7.0, 2H)	39.0, CH₂	1.88 (t, 7.0, 2H)
5'	26.2, CH₂	1.98 (q, 7.4, 2H)	26.1, CH₂	1.98 (q, 7.4, 2H)
6'	124.2, CH	5.02 (ddt, 7.0, 3.1, 1.6, 1H)	124.1, CH	5.00 (ddt, 7.1, 5.7, 1.5, 1H)
7'	130.6, C		130.6, C
8'	25.5, CH₃	1.59 (d, 1.3, 3H)	25.4, CH₃	1.56 (d, 1.5, 3H)
9'	16.0, CH₃	1.72 (d, 1.3, 3H)	15.9, CH₃	1.71 (d, 1.4, 3H)
10'	17.6, CH₃	1.52 (d, 1.3, 3H)	17.5, CH₃	1.50 (d, 1.5, 3H)
1''	174.1, CO		172.1, CO
2''	50.5, CH	4.63 (q, 7.4, 1H)	53.1, CH	3.12 (br s, 1H)
3''	16.7, CH₃	1.38 (d, 7.4, 3H)	35.0, CH₂	3.09 (d, 14.9, 1H) 3.40 (dd, 14.9, 4.7, 1H)
4''			137.8, C
5'', 9''			128.5, CH	7.23 (m, 4H)
6'', 8''			128.4, CH	7.23 (m, 4H)
7''			126.4	7.14 (tt, 5.8, 2.6, 1H)

Measured in DMSO-d₆ ^a at 125 MHz / ^b at 500 MHz.

^c Assigned based on HMBC and HSQC spectra.

Compound 2 was obtained, similar to 1, as a brown amorphous solid. The HRESIMS of 2 established its molecular formula to be C₂₈H₃₃NO₅ by revealing two peaks for a protonated molecule at m/z 464.2438 [M + H]⁺ and a sodium adduct at m/z 486.2258 [M + Na]⁺ calculated for 464.2431 and 486.2251, respectively, indicating thirteen degrees of unsaturation exceeding 1 by four degrees. The ¹H NMR spectral data of 1 and 2 (Table 1, Figures S3, S11) interpreted the additional four degrees of unsaturation in 2 by revealing five aromatic protons at δ_H 7.23 (m, 4H) and δ_H 7.14 (tt, J = 5.8, 2.6 Hz, 1H) suggesting the presence of monosubstituted aromatic ring. Apart from this additional aromatic ring, the ¹H and ¹³C NMR spectral data of 2 came in accordance with those recorded for 1 (Table 1). The ¹H NMR and ¹H-¹H COSY spectra of 2 disclosed the presence of a geranyl side chain characterized by two olefinic protons at δ_H 5.09 (td, J = 7.2, 1.4 Hz) and at δ_H 5.00 (ddt, J = 7.1, 5.7, 1.5 Hz), which exhibited key correlation in ¹H-¹H COSY spectrum to olefinic methyl groups at δ_H 1.71 (d, J = 1.4 Hz), δ_H 1.56 (d, J = 1.5 Hz) and δ_H 1.50 (d, J = 1.5 Hz), respectively, together with three methylene groups at δ_H 3.29 (d, J = 7.2 Hz), δ_H 1.98 (q, J = 7.4 Hz) and δ_H 1.88 (t, J = 7.0 Hz). In addition, the ¹H-¹H COSY spectrum of 2 unraveled two other spin systems, one connects one aromatic proton at δ_H 7.14 to four other aromatic protons at δ_H 7.23 together with a second spin system from a methine proton at δ_H 3.12 (br s) and two diastereotopic methylene protons at δ_H 3.09 (d, J = 14.9 Hz) and at δ_H 3.40 (dd, J = 14.9, 4.7 Hz). Further confirmation for the depicted structure of 2 as an isoindolinone derivative was provided by HMBC and HSQC spectra (Fig. 2, Figure S15). The HMBC spectrum of 2 revealed key correlations from the two diastereotopic methylene protons at δ_H 3.09/δ_H 3.40 to electromagnetically equivalent aromatic carbons at δ_C 128.5 (C-5'', C-9'') that were directly correlated via HSQC spectrum to two aromatic protons at δ_H 7.23 indicating the presence of additional aromatic ring in 2 as 3-hydroxy-4-phenylbutyryl moiety. The HMBC spectrum of 2 revealed similar key correlations as in 1, which revealed the position of the geranyl side chain, methoxy group and a singlet aromatic proton (δ_H 6.68) to be located on three adjacent aromatic carbons (C5-C7) in the isoindolinone nucleus. To locate the 3-hydroxy-4-phenylbutyryl moiety, the ROESY spectrum of 2 was measured and it revealed key ROE correlations from aromatic protons at δ_H 7.23 (C-5'', C-9'') to a diastereotopic methylene group at δ_H 4.22/δ_H 4.33 (d, J = 17.0 Hz, H₂-3) indicating its binding at nitrogen atom (N-2) of the isoindolinone moiety. Based on the related structures of 1 and 2 suggesting a common biosynthetic origin, sharing a similar sole chiral center and close positive \({\text{[α]}}_{\text{D}}^{\text{20}}\) values (+ 24 and + 26, respectively), the absolute configuration of 2 was concluded to be (2''R). Consequently, compound 2 was identified as a previously undescribed isoindolinone derivative featuring 3-hydroxy-4-phenylbutyryl moiety in its structure and it was named as corallocin E.

Biological activities of compounds 1–2.

The isolated isoindolinone derivatives 1 and 2 were evaluated for their antimicrobial effects, based on the serial dilution assay method against bacteria and fungi (Table S1). Compound 1 was weakly active against Mucor hiemalis at 66.6 µg/mL whereas compound 2 was similarly active against Bacillus subtilis at 66.6 µg/mL. Nystatin and oxytetracycline were used as positive controls for fungi and bacteria, respectively. The compounds were mostly inactive in the other test microorganisms. Furthermore, cytotoxicity tests revealed that the compounds were non-cytotoxic (Table S1).

Two new isoindolinone derivatives denoted as corallocins D (1) and E (2), were isolated from the fruiting bodies of the basidiomycete H. coralloides. Isoindolinone metabolites have been already isolated many times as the major metabolites from basidiomata and even cultures of the genus Hericium (Wang et al. 2015; Wittstein et al. 2016; Ryu et al., 2021; Sum et al. 2023). It is noteworthy that the isoindolinone derivatives seem to be more abundant in the solid cultures and basidiomes (Wittstein et al. 2016; Ryu et al. 2021; Sum et al. 2023) while the submerged cultures produce benzofuranones (Sum et al. 2023).

Author Contributions: W.C.S, conceptualization, screening, isolation of compounds, structure elucidation, antimicrobial assays and preparing the original draft; D.G., isolation of compounds; M.A.A.I., ECD calculation; S.S.E., structure elucidation, correcting, editing and polishing the final draft; M.S., supervision, funding acquisition, correcting, editing, and polishing the final draft. All authors have read and agreed to the published version of the manuscript.

Funding: W.C.S. was supported by a doctoral scholarship funding from the German Academic Exchange Service (DAAD) program number 57507871. The Alexander von Humboldt (AvH) foundation funded S.S.E. via the Georg-Forster Fellowship for Experienced Researchers (Ref 3.4-1222288-EGY-GF-E).

Acknowledgement: We deeply thank Wera Collisi for assistance with the bioassays, Christel Kakoschke for conducting the NMR spectroscopic measurements, as well as Aileen Gollasch and Esther Surges for running the LC-MS samples. We also thank Joette Crosier and her colleagues of KÄÄPÄ Biotech, Finland for providing the mushroom material.

Institutional Review Board Statement: Not applicable.

Informed Consent Statement: Not applicable.

Data Availability Statement: Not applicable.

Conflicts of Interest: The authors declare no conflict of interest.

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New isoindolinone derivatives isolated from the fruiting bodies of the basidiomycete Hericium coralloides

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Abstract

Figures

Introduction

Materials and methods

General experimental procedures

Fungal Material

Extraction of metabolites

Isolation of compounds 1 and 2

Antimicrobial assay

Cytotoxicity assay

Computational functional theory calculations

Results and Discussion

Conclusions

Declarations

References

Supplementary Files

Status:

Journal Publication

Version 1