Three new bioactive natural products from the fungus Talaromyces assiutensis JTY2

Article abstract of DOI:10.1016/j.bioorg.2019.103362

A novel cyclopentenone derivative, talarocyclopenta A (1), a new phenolicethers derivative, talarocyclopenta B (2) and a new itaconic acid derivative, talarocyclopenta C (3) together with four known itaconic acid derivatives (4–7) were isolated from the Talaromyces assiutensis JTY2. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. Among them, talarocyclopent (1) is the first represent an unusual type of cyclopentenone derivative, possessing a cyclopentenone unit, a 2-butanone unit and a 3-hydroxybutyric acid unit. All isolated compounds were evaluated for their anti-inflammatory and antibacterial activities. Compounds 1–4 showed inhibitory activities against the nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro. Compound 2 showed broad spectrum antibacterial against six terrestrial pathogenic bacteria.

Full text of DOI:10.1016/j.bioorg.2019.103362

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Three new bioactive natural products from the fungus Talaromyces assiuten-
sis JTY2
Jin Cai, Xue-Ming Zhou, Xing Yang, Min-Min Tang, Qi-Ying Liao, Bo-Zhen
Meng, Shan Liao, Guang-Ying Chen
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Please cite this article as: J. Cai, X-M. Zhou, X. Yang, M-M. Tang, Q-Y. Liao, B-Z. Meng, S. Liao, G-Y. Chen,
Three new bioactive natural products from the fungus Talaromyces assiutensis JTY2, Bioorganic Chemistry
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Three new bioactive natural products from the fungus
Talaromyces assiutensis JTY2
Jin Cai1,3,†, Xue-Ming Zhou1,2,3,†,, Xing Yang , Min-Min Tang , Qi-Ying Liao ,
1,3
1,3
1,3
1
, 3
1, 3
1,3,
Bo-Zhen Meng , Shan Liao , Guang-Ying Chen
1
Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of
Education, College of Chemistry & Chemical Engineering, Hainan Normal
University, Haikou, 571158, People’s Republic of China;
2
Key Lab of Functional Molecular Engineering of Guangdong Province, South China
University of Technology, Guangzhou, 510641, People’s Republic of China;
3
Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College
of Chemistry and Chemical Engineering, Hainan Normal University, Haikou,
5
71158, People’s Republic of China
Corresponding author. Tel.: (86)89865889422; fax: (86)89865889422.
E-mail address: xueming2009211@126.com, chgying123@163.com
†
These authors contributed equally to this work
1

Abstract:
A novel cyclopentenone derivative, talarocyclopenta A (1), a new phenolicethers
derivative, talarocyclopenta B (2) and a new itaconic acid derivative, talarocyclopenta
C (3) together with four known itaconic acid derivatives (4-7) were isolated from the
Talaromyces assiutensis JTY2. Their structures were elucidated by the detailed
analysis of comprehensive spectroscopic data. Among them, talarocyclopent (1) is the
first represent an unusual type of cyclopentenone derivative, possessing a
cyclopentenone unit, a 2-butanone unit and a 3-hydroxybutyric acid unit. All isolated
compounds were evaluated for their anti-inflammatory and antibacterial activities.
Compounds 1-4 showed inhibitory activities against the nitric oxide (NO) production
induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro.
Compound 2 showed broad spectrum antibacterial against six terrestrial pathogenic
bacteria.
Keywords: Talaromyces assiutensis; cyclopentenone derivative; phenolicethers
derivative; itaconic acid; anti-inflammatory activity; antibacterial activity
2

1
. Introduction
Marine microorganisms, especially marine fungi are well known as rich sources of
new natural products with promising biological and pharmacological activities [1-3].
Chemical investigations of mangrove-derived endophytic fungi, especially those from
the subtropical island of Hainan, P. R. China, have shown a sharp increase in recent
years [4-6]. As a result of adaptation to some special environments mangrove
endophytic fungus have formed unique genetic backgrounds and metabolic pathways
[7-9]. Fungi in the genus Talaromyces produce various bioactive metabolites, such as
cyclic peptides, azaphilones, meroterpenoids and butenolides [10-13]. In our
investigation on natural antibacterial and anti-inflammatory products from mangrove
fungi in the South China Sea, a fungus Talaromyces assiutensis JTY2 obtained from
the leaves of Ceriops tagal attracted our attention. The EtOAc extract of a solid rice
fermentation of the fungus exhibited antimicrobial activities and anti-inflammatory
activities. Bioassay-guided fractionation of the bioactive extract led to the isolation of
novel cyclopentenone derivative, talarocyclopenta A (1), a new phenolicethers
derivative, talarocyclopenta B (2) and a new itaconic acid derivative, talarocyclopenta
C (3) together with four known itaconic acid derivatives asperitaconic B (4) [14],
(3S)-9-hydroxy-3-carboxy-2-methylenenonanoic
acid
(5)
[15],
(3S,8R)-8-
hydroxy-3-carboxy-2-methylenenonanoic acid (6) [15] and (2S)-Butylitaconic acid
(7) [16] (Fig. 1). Compounds 1-4 showed inhibitory activities against the nitric oxide
(NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7
cells in vitro. Compound 2 showed broad spectrum antibacterial against six terrestrial
pathogenic bacteria. Herein, we report the isolation, structure elucidation and
biological activities of these compounds.
2
. Experimental
2
.1 General Experimental Procedures
3

IR spectra were recorded on a Nicolet 6700 spectrophotometer. Optical rotations
were measured on a JASCO P-1020 digital polarimeter. NMR spectra were recorded
on a Bruker AV spectrometer (400 MHz for H and 100 MHz for 13C) and a
1
1
13
JNM-ECZS spectrometer (600 MHz for H and 150 MHz for C). TMS was used as
an internal standard. HRESIMS spectra were measured on a Q-TOF Ultima Global
GAA076 LC mass spectrometer.Semi-preparative HPLC was performed on an
Agilent 1260 LC series with a DAD detector using an Agilent Eclipse XDB-C18
column (9.4 × 250 mm, 5 µm), Silica gel (Qing Dao Hai Yang Chemical Group Co.;
2
00–300 mesh), octadecylsilyl silica gel (YMC; 12 nm–50 μm) and Sephadex LH-20
GE) were used for column chromatography (CC). Precoated silica gel plates (Yan
Tai Zi Fu Chemical Group Co.; G60, F-254) were used for thin layer chromatography
TLC).
(
(
2
.2 Fungal Materials
The fungus JTY2 was isolated from the leaves of Ceriops tagal, which were
collected in the South China Sea in August, 2016. The fungal strain was deposited in
the Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education,
College of Chemistry and Chemical Engineering, Hainan Normal University of P. R.
China, Hainan with an accession number JN899320.1.
The fungus was identified according to its morphological characteristics and a
molecular biological protocol by 18S rRNA amplification and sequencing of the ITS
region. The sequence data have been submitted to GenBank, with an accession
number JN899320.1, and the fungal strain was identified as Talaromyces assiutensis.
2
.3 Extraction and isolation
The fungal strain was cultivated in 16 Kg grown on solid rice cultures in 1 L
Erlenmeyer (amount: 200; to 80 g commercially available rice was added 80 mL of
4

brine water and kept overnight prior to autoclaving) at 25 °C without shaking for 30
days. The fermentation was extracted three times with an equal volume of EtOAc.
The combined EtOAc layers were evaporated to dryness under reduced pressure to
give an EtOAc extract (254 g), which was subjected to silica gel column
chromatography (CC) (petroleum ether, EtOAc, MeOH v/v, gradient) to generate nine
fractions (Frs. 1−8). Fr. 3 was isolated by CC on silica gel eluted with petroleum
ether−EtOAc (from 50:1 to 1:1) to afford four subfractions (3a–3d). Subfraction 3b
was further purified by using octadecylsilyl silica gel (45% MeOH/H O) to obtain 1
2
(11 mg). Subfractions 3c was further separated by Semi-Preparative HPLC
(
CH CN/H O, 40: 60 v/v) to obtain 3 (13 mg), 4 (15 mg), 5 (8 mg), 6 (7 mg) and 7 (4
3
2
mg), respectively. Fr. 4 was isolated by CC on silica gel eluted with petroleum
ether−EtOAc (from 50:1 to 1:1) and then subjected to repeated Sephadex LH-20 CC
eluting with mixtures of CHCl −MeOH (1:1) to afford three subfractions (4a–4c).
3
Subfractions 4c was further separated by Semi-Preparative HPLC (CH CN/H O, 30:
3
2
7
0 v/v) to obtain 2 (6 mg).
2
.4 Physio-chemical properties of compounds 1-3
Talarocyclopenta A (1): colorless gum; [α]25 +32.8 (c 2.0, MeOH); UV (MeOH)
D
-1
1
13
λmax (log ε) 243 (2.5) nm; IR (KBr) νmax 3365, 2928, 1713 and 1634 cm ; H and C
+
NMR see Table 1 and 2; HR-ESI-MS m/z 319.1163 [M + Na] calcd for C H O Na,
1
5
20
6
3
19.1158.
-Methyl-2-oxo-5-(2-oxobutyl)cyclopent-3-enecarboxylic acid (1a): colorless gum;
3
1
13
-
H and C NMR see Table 1 and 2; HR-ESI-MS m/z 209.0815 [M - H] calcd for
C H O , 209.0819.
1
1
13
4
Talarocyclopenta B (2): colorless gum; [α]25 +28.6 (c 2.0, MeOH); UV (MeOH)
D
λmax (log ε) 356 (1.2), 272 (2.3), 210 (3.8) nm; IR (KBr) νmax 3418, 1766, 1452 and
5

−
1
1
13
-
1
384 cm ; H and C NMR see Table 1 and 2; HR-ESI-MS m/z 225.0731 [M - H]
calcd for C H O , 225.0736.
1
1
13
5
Talarocyclopenta C (3): colorless gum; [α]25 +7.4 (c 2.0, MeOH); ECD (c
D
-4
2
.5×10 mol/L, MeOH) λ (Δε) 216 (2.3), 261 (0.2); UV (MeOH) λmax (log ε) 215
max
1
13
(
3.2) nm; IR (KBr) νmax 3421, 2925, 1644, and 1118; H and C NMR see Table 1
+
and 2; HR-ESI-MS m/z 287.1497 [M + H] calcd for C H O , 287.1495.
1
4
23
6
2
.6 Antibacterial activity assay
Compounds 1–7 was tested for their antibacterial activity against six terrestrial
pathogenic bacteria Micrococcus tetragenus (ATCC 13623), Staphylococcus aureus
ATCC 8799), Staphylococcus albus (ATCC 8799), Bacillus cereus (ATCC 14579),
(
Bacillus subtilis (ATCC 6633), Escherichia coli (ATCC 25922) using a 96-well
plate-based method [17], and ciprofloxacin was used as the positive control.
2
.7 Anti-inflammatory activity
The RAW 264.7 cells were incubated in RPMI 1640 medium containing 10% fetal
bovine serum, 2 mmol/L glutamine, 100 U/mL penicillin, and 100 μg/mL
5
streptomycin. Cell concentration was adjusted to 5 × 10 cells/mL, and 200 μL of cell
suspension was seeded in each well of a 96-well plate. After 1 h incubation, cells
were treated with LPS (1 μg/mL) and test samples were dissolved in DMSO at
concentrations of 0.0625, 0.32, 1.6, 8 and 40 μM (final DMSO concentration 0.2%, v/
v) for 24 h at 37 °C. A 100 μL sample of the culture supernatant was determined by
the Griess reaction [18] The Griess reagent (50 μL of 1% sulfanilamine in 5% H PO ,
3
4
and 50 μL of 0.1% N-1-naphthylethylenediamine dihydrochloride) was added to each
well. After 10 min, the reaction products were colorimetrically quantitated at 540 nm
using a microplate reader. The experiments were performed in triplicate.
Hydrocortisone was used as a positive control; The cytotoxicity assay was performed
using the MTT method in 96-well microplates [19]. An MTT solution (200 μg/mL)
6

was added after the 24 h treatment and then incubated for another 4 h at 37 °C. The
reduced MTT-formazan was solubilized with 150 μL of DMSO, and the absorbance
of the MTT-formazan solution at 570 nm was measured by an immunoreader. The
percentage of suppression was calculated by comparing the absorbance of sample
treated cells with that of nontreated cells.
2
.8 Statistical analysis
All experiments were carried out in triplicate, and each experiment was repeated
three times. Data analysis was carried out using SPSS statistical package version 22.0
SPSS, Inc.). Differences between the test and control groups were analyzed by
t-tests. The IC values (the concentration of drug necessary to induce 50% inhibition)
(
5
0
were measured for all of the tested drugs using the Probit test in SPSS software.
2
.9 hydrolysis of talarocyclopent (1)
Acid hydrolysis of talarocyclopenta A (1): A solution of 1 (6 mg) in 5% H SO
2
4
(2 mL) was heated under reflux for 3h. The mixture was separated by the
semi-preparative HPLC to obtain a 3-hydroxybutyric acid (1.5 mg) and
3
-methyl-2-oxo-5-(2-oxobutyl)cyclopent-3-enecarboxylic acid (1a) (2.8 mg).
3
. Results and discussion
3
.1 Structure elucidation
Compound 1 was isolated as colorless gum. Its molecular formula of C H O was
1
5
20
6
+
determined by HR-ESI-MS (calcd for [M + Na] 319.1158, found 319.1163). The
1
3
H-NMR data revealed one olefinic proton δ 7.27 (br s), three sp methine signals at
H
3
δ 5.34 (m), 3.55 (m) and 2.96 (d, J = 2.8 Hz), three sp methylene signals at δ
H
H
2
7
1
.72/2.55, 2.68/2.61 and 2.43 (q, J = 7.2 Hz) and three methyl groups δ 1.05 (t, J =
H
1
3
.2 Hz), δ 1.35 (d, J = 6.4 Hz) and δ 1.75 (s). The C NMR/135DEPT data showed
H
H
5 resonances, including two carbonyls (δ 209.1, 202.3), two carboxyls (δ 174.5,
C
C
7

3
1
5
68.0), two olefinic carbons (δ 160.8, 140.4), three sp methine carbons (δ 68.7,
C C
3
8.4 and 38.8), three sp methylene carbons (δ 45.8, 40.8 and 36.2) and three methyl
C
1
1
carbons (δ 19.8, 10.3 and 7.8). The H- H COSY correlation of H-4'/H-3'/H-2'
C
combined with the HMBC correlations from H-2' to C-1' indicated the presence of a
1
1
3
-hydroxybutyric acid unit in 1 (Fig. 2). The H- H COSY correlation of H-1/H-2,
H-4/H-5/H-6 and H-5/H-9 combined with the HMBC correlations from H-10 to
C-7/8/9, from H-2/4 to C-3 and from H-6 to C-7/11 indicated the presence of a
3
-methyl-2-oxo-5-(2-oxobutyl)cyclopent-3-enecarboxylic acid unit in 1. The location
of the 3-hydroxybutyric acid unit at C-11 was confirmed by the HMBC correlation
from H-3' to C-11. The relative configuration of 1 was assigned on the basis of
NOESY correlation. The NOESY correlation of H-6/H-4 indicated that H-6 and C-4
were on the same face (Fig. 3). The acidic hydrolysis of 1 afforded a
(
+)-(S)-3-hydroxybutyric acid (1b). It was confirmed by the NMR data and [α]25
D
+
24.8, c 2.0, H O (authentic sample: [α]20D +25.1, c 1.5, H O). In addition, a
2 2
3
-methyl-2-oxo-5-(2-oxobutyl)cyclopent-3-enecarboxylic acid (1a) (The NMR data
of 1a see tables 1 and 2) was also obtained. Thus, compound 1 was identified as a
novel cyclopentenone derivative, which is the first represent an unusual type of
cyclopentenone derivative, possessing a cyclopentenone unit, a 2-butanone unit and a
3
-hydroxybutyric acid unit. We named compound 1 talarocyclopenta A.
Compound 2 was also isolated as colorless gum. The HR-ESI-MS showed a
-
molecular ion at m/z 225.0731 [M - H] calcd for C H O , 225.0736, which agreed
1
1
13
5
with molecular formula C H O . The H and 13C NMR spectra also showed a
1
1
1
14
5
3
2
-hydroxybutyric acid signal δ : 1.32 (d, J = 6.0 Hz), 4.69 (m), 2.63/2.80 and δ :
H C
0.0, 42.0, 74.1, 173.9. In addition, there are a 1,2,3-trisubstituted benzene and a
methoxy signals δ : 6.60 (dd, J = 8.4, 8.0 Hz), 6.50 (dd, J = 8.4, 1.2 Hz), 6.48 (dd, J =
H
8
.0, 1.2 Hz), 3.69 (s) and δ : 147.2, 146.8, 137.6, 119.8, 111.0, 110.2, 52.3. These
C
data closely resembled those of 3-(2,3-dihydroxyphenoxy)-butanoic acid [20] except
8

for the presence of one methoxy signal (δ 52.3 and δ 3.69, s) in 2. The location of
C
H
the methoxy group at C-1' was further confirmed by the HMBC correlation between
H-5' and C-1'. The stereo configuration of 3'-OH was assigned by comparison of the
optical rotation with the (+)-(S)-3-hydroxybutyric acid ([α]25 +28.6 vs [α]20 +25.1),
D
D
and the same biosynthetic pathway with those of 1. Thus the stereo configuration of
'-OH was assigned S-form. Hence, the structure of 2 was determined, and named as
3
talarocyclopenta B.
Compound 3 was also obtained as colorless gum, a molecular formula of C H O ,
1
4
22
6
+
was determined by HRESIMS signals at m/z 287.1497 [M + H] (cald for C H O
23 6,
1
4
1
2
87.1495). The H-NMR data revealed two olefinic proton δ 6.14 (s) and 5.51 (s),
H
3
3
one sp methine signal at δ 3.52 (t, J = 7.2 Hz), six sp methylene signals at δ
H
H
1
3
1
.30-1.82 (10H), 4.04 (2H, t, J = 6.4 Hz) and one methyl group δ 2.02 (s). The C
H
NMR/135DEPT data showed 14 resonances, including three carboxyls (δ 176.4,
C
3
1
74.0 and 173.1), two olefinic carbons (δ 144.5 and 123.4), one sp methine carbon
C
3
(
δ 48.6), six sp methylene carbons (δ 26.8-32.4 and 65.7) and one methyl carbon
C
C
(
δC 20.8). These data including optical rotation ([α]25 +7.4) closely resembled those
D
of known compound 4 ([α]25 +7.70, c 2.50 MeOH) [14] except for the presence of
D
one methoxy signal (δ 52.2 and δ 3.64, s) in 3. The location of the methoxy group at
C
H
C-1 was further confirmed by the HMBC correlation between H-14 and C-1.Thus the
stereo configuration of 3 was assigned S-form. Further more, the experimental ECD
spectrum of 3 (Fig. 4) showed two positive (216 nm) and (261 nm) Cotton effects.
The calculated ECD spectrum (the ECD calculation details see supporting
information) for the (S) enantiomer showed a similar ECD curve. The above
information allowed the determination of the absolute configuration of 3 as S. Herein
the structure of 3 was established, and named as talarocyclopenta C.
The structures of known compounds 4−7 were identified by comparison of their
spectroscopic data with those in the literature.
9

3
.2 Antibacterial activity
Compounds 1–7 were evaluated for their antibacterial activities against six
pathogenic bacteria including M. tetragenus, S. aureus, S. albus, B. cereus, B.subtilis,
E. coli. Compound 2 show broad spectrum antibacterial against six terrestrial
pathogenic bacteria, and 1 exhibited weak antibacterial activities (table 3), The MIC
values of other compounds higher than 40 μg/mL were regarded as inactive.
3
.2 Anti-inflammatory activity
Compounds 1–7 were evaluated their anti-inflammatory activities via testing the
inhibitory activities against the nitric oxide (NO) production induced by
lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro. As a result,
compounds 1-4 showed significant inhibitory activities with the IC value of 3.38 ±
5
0
0
.12 μM, 6.26 ± 0.10 μM, 12.56 ± 0.08 μM and 15.63 ± 0.12 μM, respectively. While
the positive control, hydrocortisone, showed a inhibitory activity with the IC value
5
0
of at 3.68 ± 0.10 μM. No cytotoxicity was observed in compounds 1-4 treated cells
(
cell viability > 85%). The IC values of other compounds higher than 40 μM were
50
regarded as inactive.
4
. Conclusions
In this study, A novel cyclopentenone derivative, talarocyclopenta A (1), a new
phenolicethers derivative, talarocyclopenta B (2) and a new itaconic acid derivative,
talarocyclopenta C (3) together with four known itaconic acid derivatives (4-7) were
isolated from the Talaromyces assiutensis JTY2. talarocyclopenta A (1) is the first
represent an unusual type of cyclopentenone derivative, possessing a cyclopentenone
unit, a 2-butanone unit and a 3-hydroxybutyric acid unit. It presence as characteristic
marker may be helpful in chemotaxonomical classifications. The significant inhibitory
activities on NO production of compounds 1-4 and antibacterial activities of
compound 2 could be used for the development of new anti-inflammatory and
1
0

antibacterial agents.
Conflict of interest
The authors have declared that there is no conflict of interest.
Acknowledgements
This work was supported by the Hainan Province Natural Science Foundation
(
218QN234), the Hainan Province Natural Science Foundation of Innovative Research
Team Project (2016CXTD007), the Innovative Research Team Project of Ministry
IRT-16R19), the open foundation of Key Laboratory of Functional Molecular
(
Engineering of Guangdong Province (No. 2018kf08) and College Students’
Innovative Training Program of Hainan Normal University (cxcyxj2018018).
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1
2

O
5
O
O
O
O
5'
3
'
3
OH
3
O
1
1
'
O
HO
OH
1'
9
O
HO
O
3'
O 7
5
1
O
2
1
0
1
1
a
O
O
O
1
3
HO 4
HO
HO
3
O
9
7
5
O
O
OH
R O
2
1
R
1
OH
OH
3
4
5
R = OMe R = Ac
1 2
R = OH R = Ac
1
2
6
7
R = OH R = H
1
2
Fig. 1 The Structure of compounds 1–7 and 1a
1
3

O
O
O
OH
O
O
HO
O
OH
O
O
O
HO
O
O
O
O
1
2
3
1
1
Fig. 2 Key H- H COSY and HMBC correlations for Compounds 1–3
1
4

Fig. 3 Key NOESY correlations for Compound 1
1
5

Fig. 4 Experimental ECD spectra (200400 nm) of JTY in MeOH and the calculated
ECD spectra of the model molecules of 3 at the B3LYP/6-311+G(d, p) level..
1
6

1
Table 1. H NMR Data (δ in ppm, J in Hz ) of compounds 1–3 (400 MHz) and 1a/1b (600
MHz)
1a
1a (1-11)/1b (1'-5')a
2b
3b
position
δ
H
(J in Hz)
δ
H
(J in Hz)
δ
H
(J in Hz)
1
2
3
1.05 (t, 7.2)
2.43 (q, 7.2)
-
1.07 (t, 7.2)
2.44 (q, 7.2)
-
-
-
-
3.52 (t, 7.2)
-
2
.68 (dd, 8.0, 4.0)
2.71 (dd, 17.4, 7.2)
4
6.50 (dd, 8.4, 1.2)
-
2
.61 (d, 8.0)
3.55 (m)
2,60 (dd, 17.4, 8.4)
5
6
7
8
9
3.59 (m)
6.60 (dd, 8.4, 8.0)
1.82/1.70 (m)
1.34 (m)
1.34 (m)
1.34 (m)
1.61 (m)
4.04 (t, 6.4)
-
2.96 (d, 2.8)
3.01 (d, 3.0)
6.48 (dd, 8.0, 1.2)
-
-
-
-
-
-
7.27 (br s)
7.29 (m)
-
1
1
0
1
1.75 (s)
1.78 (t, 1.2)
-
-
-
-
-
1
2
3
'/12
'/13
'/14
-
-
2.02 (s)
2
2
.72 (dd, 10.0, 6.0)
.55 (dd, 10.0, 2.4)
5.34 (m)
2.59 (dd, 18.0, 6.6)
2.49 (dd, 18.0, 8.4)
4.54 (m)
2.80 (dd, 12.0, 8.0)
2.63 (dd, 12.0, 4.8)
4.69 (m)
6.14/5.51 (s)
3.64 (s)
4
5
'
'
1.35 (d, 6.4)
-
1.32 (d, 6.0)
-
1.32 (d, 6.0)
3.69 (s)
-
-
a
Measured in CDCl3.
b
Measured in CD OD
3
.
1
7

1
3
Table 2. C NMR Data (δ in ppm, J in Hz ) of compounds 1–3 (100 MHz) and 1a/1b (150
MHz)
position
1a
1a (1-11)/1b (1'-5')a
2b
3b
δ
C
, type
δ
C
, type
δ
C
, type
1
2
3
4
5
6
7
8
9
7.8, CH
36.2, CH
209.1, C
3
7.8, CH
36.2, CH
208.8, C
3
147.2, C
176.4
2
2
137.6, C
48.6, CH
144.5, C
173.1, C
146.8, C
45.8, CH
38.8, CH
58.4, CH
202.3, C
160.8, C
140.4, CH
2
46.0, CH
38.9, CH
58.2, CH
201.9, C
160.3, C
140.5, CH
2
111.0, CH
119.8, CH
32.4, CH
29.6, CH
28.7, CH
26.8, CH
30.1, CH
65.7, CH
2
110.2, CH
2
2
2
2
2
-
-
-
1
1
0
1
10.3, CH
3
10.4, CH
3
-
168.0, C
174.5, C
169.3, C
174.9, C
-
174.0, C
1
2
3
'/12
'/13
'/14
173.9, C
20.8, CH
3
40.8, CH
2
45.6, CH
2
42.0, CH
2
123.4, CH
68.7, CH
65.1, CH
74.1, CH
52.2, CH
3
4
5
'
'
19.8 CH
3
22.2 CH
3
20.0, CH
3
-
-
-
-
52.3, CH
3
a
Measured in CDCl3.
b
Measured in CD OD
3
.
1
8

Table 3 Antibacterial activity of 1–2
MIC values (μg/mL)
Compounds
M. tetragenus
S. aureus
S. albus B. cereus
B. subtilis
E. coli
1
>40
5
20
2.5
>40
5
>40
2.5
>40
2.5
40
2
1.25
0.625
Ciprofloxacina
0.313
0.313
0.625
0.625
0.625
a
Ciprofloxacin was used as a positive control.
1
9

2
0

Highlights
Three new Bioactive natural products from the Fungus Talaromyces assiutensis sp.
JTY2.
Compound 1 is the first represent an unusual type of cyclopent derivative.
The anti-inflammatory activities and antibacterial activities of all isolated compounds
were evaluated in vitro.
Compounds 1-4 exhibited significant inhibitory effects against the nitric oxide (NO)
production induced by lipopolysaccharide.
Compound 2 showed broad spectrum antibacterial against six terrestrial pathogenic
bacteria.
2
1