Introduction

Fungi are considered as a potential repository that we depend on in our endeavors for the discovery of pharmacologically important molecules with notable bioactivities or druggability to some extent. Chaetomium genus, containing more than 100 species, is a common fungal genus that ubiquitously inhabited in soil and decomposed plant materials. A large number of structurally diverse metabolites have recently been characterized from Chaetomium species, including chaetoglobosins, xanthones, anthraquinones, azaphilones, terpenoids, and steroids [1, 2]. These structures display a wide range of biological activities, such as anticancer, antimicrobial, enzyme inhibitory, antimalarial, and antioxidant [1].

Previously, we reported the isolation and characterization of biologically active metabolites from Chaetomium species, including anticancer molecules from Chaetomium globosum [3], and antifungal agents from Chaetomium seminudum [4]. Encouraged by these discoveries, two strains namely C. seminudum C208 and Chaetomium sp. C521 were selected for further investigation. After repeated column chromatograph, 15 polyketide metabolites 1−15 including four new ones chaetosemins G-J (1−4) were obtained (Fig. 1). In details, compounds 1−9 were produced by C. seminudum, and 10−15 were isolated from Chaetomium sp., respectively. Herein, we addressed the isolation, structure determination, and bioactivity evaluation of these metabolites.

Fig. 1
figure 1

Structures of compounds 1−9 from C. seminudum. C208 and 10−15 from Chaetomium sp. C521

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Results and discussion

Chaetosemin G (1) obtained as a white powder has the molecular ion at m/z 243.0424 ([M+H]+) by its HR-ESIMS, indicating its molecular formula to be C11H11O4Cl. The 1H NMR spectrum showed the presence of one methine signal at δH 4.67, one methylene group at δH 2.79 (dd, J = 16.6, 11.6 Hz) and 3.15 (dd, J = 16.8, 3.3 Hz), and two methyl groups at δH 1.56 (d, J = 6.3 Hz) and δH 2.19 (Table 1). The 13C NMR spectrum combined DEPT and HSQC experiments demonstrated that 1 was similar to monaschromone (5) except for the downfield movement of C-5 (from δC 105.5 to 109.2). Further analysis of 2D NMR spectrum including 1H−1H COSY, HSQC, and HMBC spectra indicated that 1 was a chlorinated monaschromone (5) [5] at C-5, which rationalized all the 1H and13C NMR spectral data. The stereochemistry of 1 was determined as 2S-configuration since the optical rotation of 1 ([α]D28+124.16, CH3OH) agreed with that of monaschromone ([α]D25 = +34.4, CH3Cl; [α]D20 = +74.55, CH3OH) [5]

Table 1 1H and 13C NMR data for 1–4
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Chaetosemin H (2), isolated as a white powder, possessed a molecular formula of C11H12O5 based on the [M + Na]+ peak at m/z 247.0572 in its HRESIMS. The 1H NMR spectrum of 2 gave altogether four singlets at δH 6.35, 3.69, 2.54, and 2.07, and its 13C NMR spectrum displayed 11 resonance lines ascribed to six aromatic carbons, two carbonyls and two methyl groups (Table 1). Close analysis of the 1H and 13C NMR spectra of 2 disclosed that they resembled those of 6-methylcurvulinic acid [6]. This observation was supported by the subsequent 2D NMR (COSY, NOESY, HMQC and HMBC), leading to the unambiguous assignment of all 1H and13C NMR data of 2. In particular, the key HMBC correlations of CH3-11 (δH 2.07) with C-6 (δC 159.66) and C-8 (δC 134.69) demonstrated that 2 was 7-methylcurvulinic acid.

Chaetosemin I (3) was obtained as a colorless amorphous powder, and the molecular formula was deduced to be C10H14O3 from its molecular ion at m/z 183.1013 ([M + H]+) by HR-ESIMS. IR absorptions implied that 3 possessed hydroxy group (3381 cm−1) and an aromatic ring (1627, 1594 cm−1). The 1H and 13C NMR spectra (δH/δC2.00/8.31; δH/δC 6.19 × 2/108.66 × 2, 109.90, 138.24, and 157.01 × 2) indicated that 3 was a 1,2,3,5-tetrasubstituted benzene derivative with a 1,3-dihydroxy-2-methylphenol ring (Table 1), whose data were similar to those of the 1,3-dihydroxyphenol ring in orcinotriol [7]. 1H–1H COSY connectivities of H-1 to H-2 and H-2 to H-3 suggested the presence of a 2-hydroxypropyl group. The structure of 3 was next confirmed by the HSQC, 1H−1H COSY, and HMBC experiments, especially the correlations of CH3-10 with C-6 and C-8, of H-5 with C-3, and of CH3-1 with C-3. Thus, compound 3 was determined as 7-methylorcinotriol [7]. Comparison of the specific rotations of 3 ([α]D28+12, CH3OH) with that of (2S)-orcinotriol ([α]D25+6, CH3OH), which was isolated from the culture of the yeast Aureobasidium pullulans [7], suggested the absolute configuration at C-2 of 3 to be S.

Chaetosemin J (4), afforded as a white powder, has a quasi-molecular ion at m/z 245.0817 ([M-H]−) by its HR-ESIMS, indicating its molecular formula to be C14H14O4. The 1H NMR spectrum showed three aromatic proton NMR signals at δH 6.22 (2 H, d, J = 2.1 Hz) and 6.20, suggesting the incorporation of a 1,3,5-trisubstituted benzene unit in the molecule (Table 1). The 13C NMR resonance profile disclosed the presence of the α, β-unsaturated ketone moiety on the basis of the signals at δC 182.4, 164.8 and 169.9. Moreover, the 1H and 13C NMR spectra data indicated that it was close to macrocarpon C [8]. The only difference in 4 was the presence of a singlet at δH 1.92 (CH3-14) in the 1H NMR spectrum. The subsequent analysis of its 2D NMR spectra, especially the key HMBC correlations of CH3-1 with C-3, of CH3-14 with C-4, and of CH2-7 with C-5, and C-9 pinpointed that compound 4 was a 3-methylated derivative of macrocarpon C.

In addition, the known compounds were identified as monaschromone (5) [5], chaetoquadrin F (6) [9], monorden A (7) [10], pseurotin A (8) [11], decarestrictine D (9) [12], mollipilin A (10) [13], epicoccone B (11) [14], (–)-aureonitol (12) [15], chaetoglocin A (13) [15], 1,2-benzenedicarboxaldehyde-3,4,5-trihydroxy-6-methyl (flavipin, 14) [16], chaetoglobosin B (15) [17], by comparison of their spectroscopic data with the literature. Interestingly, decarestrictine D (tuckolide, 9), isolated from Polyporus tuberaster [18] and Penicillium corylophilum [12] was found to exert inhibitory activity against cholesterol biosynthesis but no other effects, such as antibacterial or antifungal activities.

All the isolated compounds were subjected to bioactive assays, including antifungal, brine shrimp toxicity, antioxidant, and α-glucosidase inhibitory activity as previously reported method [4, 19, 20]. All 15 metabolites except 8 were tested in vitro for the antifungal activity against the phytopathogenic fungi Botrytis cinerea, Alternaria solani, Magnaporthe oryzae, and Gibberella saubinettii. Some of them displayed varying degrees of antifungal activities against several plant pathogenic fungi. Among the tested compounds (1, 3−4) showed significant antifungal activities (minimum inhibitory concentrations (MICs) = 6.25–50.0 μM). Compound 3 displayed moderate inhibitory activity against B. cinerea with the MIC value of 12.5 μM, and 4 exhibited inhibitory activity against B. cinerea, A. solani, M. oryzae, and G. saubinettii, with MIC values of 25, 12.5, 12.5, and 25 μM, respectively. Notably, compound 5 inhibited the growth of B. cinerea, A. solani, M. oryzae, and G. saubinettii, with the MIC values of 12.5, 12.5, 12.5, and 6.25 μM, which were comparable to the commonly used fungicide carbendazim, indicating that it could be used as a fungicide or as a lead compound of new fungicides.

In this assay, only compound 1 possessed a weak lethality activity toward brine shrimps (Artemia salina) with corrected mortality rate 57.8% at 100 μM, while the positive control toosendanin giving 100% corrected mortality rate at 1.0 μM, while others including 14 did not display any effects.

Compounds 11 and 14 presented the moderate antioxidant activity with regard to DPPH radical scavenging ability, with IC50 values of 10.8 and 7.2 μM, respectively, compared to that of the positive control ascorbic acid (IC50 = 6.5 μM). The antioxidant ability of compound 14 was consistent with the results reported [16].

Moreover, in the α-glucosidase inhibitory activity assay, both 11 and 14 inhibited this enzyme with an IC50 values of 27.3 and 33.8 μM, respectively, which were almost 30-fold stronger than that of acarbose (IC50 = 838.3 μM), a well known drug, while other compounds (2–7, and 9) had no effects at 50 μM, and no test of compounds (1, 8) was carried out due to lack of sufficient sample. To the best of our knowledge, this is the first time that both 11 and 14 were found to have α-glucosidase inhibitory activities.

In conclusion, 15 polyketides including four new ones, namely, chaetosemins G-J (1−4) were isolated and identified from the culture of C. seminudum C208 and of Chaetomium sp. C521, respectively. In the bioassays, both epicoccone B (11) and flavipin (14) exhibited an obvious antioxidant and α-glucosidase inhibitory activities, while chaetosemin J (4) and monaschromone (5) displayed the potential antifungal effects on the test fungal pathogens. Collectively, our findings indicated that chaetosemin J (4) and monaschromone (5) might act as the lead compounds of pesticide.