Chemical investigation of the ethyl acetate extract of Corynespora cassiicola, isolated from leaf tissues of the Chinese mangrove medicinal plant Laguncularia racemosa, yielded four new secondary ...metabolites, including three decalactones, xestodecalactones D–F (1–3) as well as corynesidone C (4), in addition to four known compounds. The structures of the new compounds were determined on the basis of one‐ and two‐dimensional NMR spectroscopy as well as by high‐resolution mass spectrometry. Absolute configurations of the optically active compounds 1–3 were determined by TDDFT ECD calculations of their solution conformers, proving that they belong to the (11S) series of xestodecalactones, opposite to the (11R) configuration of the known xestodecalactones A–C. All compounds were tested against a panel of human protein kinases. Among the isolated compounds, two inhibited several kinases such as IGF1‐R and VEGF‐R2 with IC50 values mostly in the low micromolar range.
Three new xestodecalactones D–F (1–3) and a new corynesidone C were isolated from Corynespora cassiicola. The structures were determined by 1D and 2D NMR spectroscopy as well as by high‐resolution mass spectrometry. The absolute configurations of 1–3 were determined by TDDFT ECD calculations. All compounds were tested against a panel of human protein kinases.
Chemical investigation of methanol extracts from two Jordanian marine sponges belonging to genus Diacarnus: D. erythraeanus and D. ardoukobae (family Podospongiidae) afforded a series of norterpene ...cyclic peroxides namely; muqubilone A (1), sigmosceptrellin‐B (2), sigmosceptrellin‐B methyl ester (3), (+)‐methyl‐2‐epinuapapuanoate (4); (−)‐methyl‐2‐epinuapapuanoate (5) in addition to a macrolide derivative: latrunculin B (6). Chemical structures of isolated compounds were elucidated based on their 1D and 2D NMR and mass spectra as well as by comparison with the literature. All isolated compounds were assessed for their cytotoxic activity against the murine lymphoma (L5178Y) cell line. Among tested compounds, only (2–4) displayed significant cytotoxicity with IC50 values ranging from 1.2 to 6.4 μM. Molecular docking studies of isolated compounds suggested potential EGFR inhibition and the correlation between docking scores and biological data was strong based on Pearson's correlation coefficient (r=0.93).
Two Jordanian marine sponges belonging to genus Diacarnus were chemically investigated yielding five norterpene cyclic peroxides along with one macrolide derivative. In the cytotoxic assay, compounds sigmosceptrellin‐B (2), its methyl ester (3) and (+)‐methyl‐2‐epinuapapuanoate (4) displayed significant cytotoxicity with IC50 values ranging from 1.2 to 6.4 μM. Molecular docking studies suggested potential EGFR inhibition with a strong correlation between docking scores and biological data based on Pearson's correlation coefficient (r=0.93).
Dysregulation of the Wnt signaling pathway contributes to the development of many cancer types. Natural compounds produced with biotechnological systems have been the focus of research for being a ...new drug candidate both with unlimited resources and cost-effective production.
In this study, it was aimed to reveal the effects of isopropylchaetominine on cytotoxic, cytostatic, apoptotic and Wnt signaling pathways in brain, pancreatic and prostate cancer.
The IC50 values of isopropylchaetominine in U-87 MG, PANC1, PC3 and LNCaP cells were calculated as 91.94 μM, 41.68 μM, 54.54 μM and 7.86 μM in 72nd h, respectively. The metabolite arrests the cell cycle in G0/G1 phase in each cancer cells. Iso-propylchaetominine induced a 4.3-fold and 1.9-fold increase in apoptosis in PC3 and PANC1 cells, respectively. The toxicity of isopropylchaetominine in healthy fibroblast cells was assessed using the annexin V method, and no significant apoptotic activity was observed between the groups treated with the active substance and untreated. In U-87 MG, PANC1, PC3, and LNCaP cells under treatment with isopropylchaetominin, the expression levels of DKK3, TLE1, AES, DKK1, FRZB, DAB2, AXIN1/2, PPARD, SFRP4, APC and SOX17 tumor suppressor genes increased significantly. Decreases in expression of Wnt1, Wnt2, Wnt3, Wnt4, Wnt5, Wnt6, Wnt10, Wnt11, FRZ2, FRZ3, FRZ7, TCF7L1, BCL9, PYGO, CCND2, c-MYC, WISP1 and CTNNB1 oncogenic genes were detected.
All these result shows that isopropylchaetominine can present promising new treatment strategy in different cancer types.
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•Iso-propylchaetominine exhibits anticancer activity in in vitro models of brain, pancreatic and prostate cancer.•Iso-propylchaetominin arrests the cell cycle in the G0/G1 phase.•Iso-propylchaetominine regulates the Wnt signaling pathway.•Iso-propylchaetominine causes cell cycle arrest by regulating the Wnt pathway.
Co-cultivation of the endophytic fungus
Fusarium tricinctum
with
Streptomyces lividans
on solid rice medium led to the production of four new naphthoquinone dimers, fusatricinones A-D (
1-4
), and a ...new lateropyrone derivative, dihydrolateropyrone (
5
), that were not detected in axenic fungal controls. In addition, four known cryptic compounds, zearalenone (
7
), (−)-citreoisocoumarin (
8
), macrocarpon C (
9
) and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (
10
), that were likewise undetectable in extracts from fungal controls, were obtained from the co-culture extracts. The known antibiotically active compound lateropyrone (
6
), the depsipeptides enniatins B (
11
), B1 (
12
) and A1 (
13
), and the lipopeptide fusaristatin A (
14
), that were present in axenic fungal controls and in co-culture extracts, were upregulated in the latter. The structures of the new compounds were elucidated by 1D and 2D NMR spectra as well as by HRESIMS data. The relative and absolute configuration of dihydrolateropyrone (
5
) was elucidated by TDDFT-ECD calculations.
Naphthoquinone dimers from co-culture of
Fusarium tricinctum
with
Streptomyces lividans
.
Chemical investigation of the MeOH extract of the sponge Acanthostrongylophora ingens afforded the new manzamine derivative ircinal E (1), in addition to six known metabolites (2–7). The structure of ...the new compound was unequivocally elucidated using one- and two-dimensional NMR spectroscopy, as well as high-resolution mass spectrometry. Compounds 1–6 exhibited strong to moderate cytotoxicity against the murine lymphoma L5178Y cell line with IC50 values ranging from 2.8 to 21.7 μM.
Eight new hydroquinone derivatives, gliomastins A-D (
1-4
), 9-
O
-methylgliomastin C (
5
), acremonin A 1-
O
-β-
d
-glucopyranoside (
6
), gliomastin E 1-
O
-β-
d
-glucopyranoside (
7
), and 6′-
O
...-acetyl-isohomoarbutin (
8
), together with seven known analogues were isolated from the marine-derived fungus
Gliomastix
sp. Their structures were elucidated by extensive spectroscopic analysis including 1D and 2D NMR measurements aided by DFT NMR calculations as well as MS data. TDDFT-ECD and OR calculations were performed to determine the absolute configurations of
1
and the aglycones of
6
and
7
. Compound
1
features a novel skeleton, biogenetically derived from a Diels-Alder reaction between derivatives of
11
and
13
. Compound
2
represents a rare sulfur-containing alkaloid derived from the known hydroquinone
13
. Compounds
1
,
10
and
12
showed strong cytotoxicity against the L5178Y mouse lymphoma cell line with IC
50
values of 1.8, 1.0 and 1.1 μM, respectively. Compound
3
exhibited moderate antitubercular activity against
Mycobacterium tuberculosis
with a MIC value of 12.5 μM.
A novel cytotoxic quinone/hydroquinone dimer from the marine-derived fungus
Gliomastix
sp.
Chemical investigation of the EtOAc extract of the endophytic fungus Bionectria ochroleuca , isolated from the inner leaf tissues of the plant Sonneratia caseolaris (Sonneratiaceae) from Hainan ...island (China), yielded two new peptides, pullularins E and F ( 1 and 2 ) together with three known compounds ( 3 – 5 ). The structures of the new compounds were unambiguously determined on the basis of one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configurations of amino acids were determined by HPLC analysis of acid hydrolysates using Marfey’s method. The isolated compounds exhibited pronounced to moderate cytotoxic activity against the mouse lymphoma cells (L5178Y) with EC 50 values ranging between 0.1 and 6.7 µg/mL.
Chemical investigation of aerial parts of Helichrysum italicum yielded two new pyrone derivatives (1 and 2) along with ten known compounds. The structures of the new compounds were established by 1D ...and 2D NMR spectra as well as by HRESIMS data. Compound 1 represented a rare dimer of substituted α- and γ-pyrone units. DFT-NMR and TDDFT-ECD calculations were carried out to determine the absolute configuration of 1 but failed, representing the limitation of TDDFT-ECD calculation for the configurational assignment. All compounds were measured for their antibacterial and cytotoxic activity but proved to be inactive.
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