Two new diaryl ether heptanoids, giffonins J and K (1 and 2), along with five new diarylheptanoids, giffonins L-P (3-7), were isolated from a methanol extract of the leaves of Corylus avellana ...cultivar "Tonda di Giffoni". These compounds were identified as highly hydroxylated cyclized diarylheptanoids by 1D- and 2D-NMR experiments. The relative configurations of giffonins J-P (1-7) were established by a combined QM (quantum mechanical)/NMR approach, comparing the experimental (13)C/(1)H NMR chemical shift data and the related predicted values. The cytotoxic activities of giffonins J-P (1-7) were evaluated against the human osteosarcoma U2Os and SAOs cell lines.
Total Synthesis of Tedarene A Maurent, Kelly; Vanucci-Bacqué, Corinne; Saffon-Merceron, Nathalie ...
Journal of natural products (Washington, D.C.),
05/2017, Letnik:
80, Številka:
5
Journal Article
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Tedarene A is a macrocyclic diaryl ether heptanoid isolated from the marine sponge Tedania ignis showing an inhibitory effect against nitric oxide production. The first total synthesis of tedarene A ...was achieved starting from the commercially available 3-(4-methoxyphenyl)propan-1-ol in nine steps and 15.3% overall yield. The synthetic sequence featured an E,Z-dienic bond introduction and a macrocyclization under Ullman conditions. During the synthesis, the E,E-isomer of tedarene A was also obtained and fully characterized.
Efflux pumps are one of the well established mechanisms that contribute to antibiotic resistance in bacteria, such as mycobacteria. As a result, the identification of efflux pump inhibitors is an ...attractive target in antimicrobial therapy. The isolated compounds, three diarylheptanoids, trans,trans-1,7-diphenylhepta-4,6-dien-3-one (1), (5R)-trans-1,7-diphenyl-5-hydroxyhept-6-en-3-one (2), (3S,5S)-trans-1,7-diphenylhept-1-ene-3,5-diol (3) and the flavonoid pinocembrin (4), from Alpinia katsumadai, Zingiberaceae, were examined for their antimycobacterial activity and their synergistic effects with different antibiotics against M. smegmatis mc2 155. Furthermore, these compounds were evaluated as potential EtBr efflux inhibitors. Although they showed weak antimycobacterial activities (MIC⩾64mg/L), especially compound 1 revealed a significant activity on the EtBr accumulation and efflux as well as a synergistic effect in combination with rifampicin.
Turmeric extract, a mixture of curcumin and its demethoxy (DMC) and bisdemethoxy (BDMC) isomers, is used as an anti-inflammatory preparation in traditional Asian medicine. Curcumin is considered to ...be the major bioactive compound in turmeric but less is known about the relative anti-inflammatory potency and mechanism of the other components, their mixture, or the reduced in vivo metabolites. We quantified inhibition of the NF-κB pathway in cells, adduction to a peptide mimicking IκB kinase β, and the role of cellular glutathione as a scavenger of electrophilic curcuminoid oxidation products, suggested to be the active metabolites. Turmeric extracts (IC
14.5 ± 2.9 μM), DMC (IC
12.1 ± 7.2 μM), and BDMC (IC
8.3 ± 1.6 μM), but not reduced curcumin, inhibited NF-κB similar to curcumin (IC
18.2 ± 3.9 μM). Peptide adduction was formed with turmeric and DMC but not with BDMC, and this correlated with their oxidative degradation. Inhibition of glutathione biosynthesis enhanced the activity of DMC but not BDMC in the cellular assay. These findings suggest that NF-κB inhibition by curcumin and DMC involves their oxidation to reactive electrophiles, whereas BDMC does not require oxidation. Because it has not been established whether curcumin undergoes oxidative transformation in vivo, oxidation-independent BDMC may be a promising alternative to test in clinical trials.
The irrational use of medications has increased the incidence of microbial infections, which are a major threat to public health. Moreover, conventional therapeutic strategies are starting to become ...ineffective to treat these infections. Hence, there is a need to develop and characterize novel antimicrobial compounds. Phytochemicals are emerging as a safe and accessible alternative to conventional therapeutics for treating infectious diseases. Curcumin is extracted from the dried rhizome of the spice turmeric (Curcuma longa (Zingiberaceae)). However, the bioavailability of curcumin is low owing to its lipophilic property and thus has a low therapeutic efficacy in the host. A previous study synthesized structural variants of curcumin, which are called monocurcuminoids (CNs). CNs are synthesized based on the chemical structure of curcumin with only one methyl bridge. The biological activities of four previously synthesized CNs (CN59, CN63, CN67, and CN77), curcumin, and turmeric powder were examined in this study. Gas chromatography-tandem mass spectrometry analysis of curcumin and turmeric powder revealed similar peaks, which indicated the presence of curcumin in turmeric powder. The antioxidant activity of the test compounds was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays. The ABTS radical scavenging activities of the test compounds were similar to those of vitamin C. The minimum inhibitory concentration (MIC) values of the test compounds against seven microbial strains were in the range of 4.06–150 μg/mL. The MIC value was equal to minimum bactericidal concentration value for CN63 (150 μg/mL) and CN67 (120 μg/mL) against Staphylococcus aureus. The treatment combination of CN77 (8.75 or 4.37 μg/mL) and turmeric powder (9.37 or 4.68 μg/mL) exerted synergistic growth-inhibiting effects on Aeromonas hydrophila, Candida albicans, and Pseudomonas aeruginosa. Photodynamic therapy using 2X MIC of CN59 decreased the growth of Enterococcus faecalis by 4.18-fold compared to the control group and completely inhibited the growth of Escherichia coli. The results of the hemolytic assay revealed that the test compounds were not cytotoxic with half-maximal inhibitory concentration values ranging from 49.65–130.9 μM. The anticoagulant activity of most compounds was comparable to that of warfarin but higher than that of heparin. This indicated that these compounds target the intrinsic coagulation pathway. These results demonstrated that these CNs are a safe and promising alternative for curcumin.
This study led to the characterization of 27 diarylheptanoids, including 13 hitherto unknown compounds. Compound
1 and alnuside A (
27) were found to possess inhibitory activities against LPS-induced ...NO production with respective IC
50 values of 7.99 and 8.08
μM and void of significant cytotoxicity.
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► HPLC-SPE-NMR is demonstrated to be a good tool for chemical screening of natural products. ► 27 Diarylheptanoids including 13 hitherto unknown were isolated from
Alnus formosana. ► 5-
O-Butylhirusutanonol and alnuside A possess good anti-inflammatory activities without significant cytotoxicity.
This study was aimed to investigate thoroughly the diarylheptanoids in the
n-BuOH soluble fraction of leaves of
Alnus formosana in order to examine their anti-inflammatory activities. The application of HPLC-SPE-NMR as a preliminary chemical screening led to characterization of eleven compounds. Further separation resulted in isolation of 28 compounds, of which 10 diarylheptanoids and 2-coumaroylxyloside are new natural products. Compound
1 and alnuside A (
27) were found to possess good activities against LPS-induced NO production with respective IC
50 values of 7.99 and 8.08
μM, and which were devoid of significant cytotoxicity.
Eleven diarylheptanoids (1–11) were isolated from the rhizomes of Curcuma kwangsiensis, together with seven known compounds. All isolated compounds were evaluated for inhibitory activities against ...LPS-induced NO production in RAW 264.7 macrophages.
Eleven diarylheptanoids (1–11) were isolated from rhizomes of Curcuma kwangsiensis, together with seven known compounds. Their structures were elucidated by 1D and 2D NMR, circular dichroism (CD), and accurate mass measurements. Inhibitory effects of the isolated compounds on nitric oxide production in lipopolysaccaride-activated macrophages were evaluated. Compounds 1, 2, and 3 showed strong inhibitory activity on NO production with IC50 values of 3.13, 2.81 and 2.41μM, respectively.
Hematopoietic stem cells (HSCs, CD34+ cells) have shown therapeutic efficacy for transplantation in various hematological disorders. However, a large quantity of HSCs is required for transplantation. ...Therefore, strategies to increase HSC numbers and preserve HSC functions through ex vivo culture are critically required. Here, we report that expansion medium supplemented with ASPP 049, a diarylheptanoid isolated from Curcuma comosa, and a cocktail of cytokines markedly increased numbers of adult CD34+ cells. Interestingly, phenotypically defined primitive HSCs (CD34+CD38-CD90+) were significantly increased under ASPP 049 treatment relative to control. ASPP 049 treatment also improved two functional properties of HSCs, as evidenced by an increased number of CD34+CD38- cells in secondary culture (self-renewal) and the growth of colony-forming units as assessed by colony formation assay (multilineage differentiation). Transplantation of cultured CD34+ cells into immunodeficient mice demonstrated the long-term reconstitution and differentiation ability of ASPP 049-expanded cells. RNA sequencing and KEGG analysis revealed that Hippo signaling was the most likely pathway involved in the effects of ASPP 049. These results suggest that ASPP 049 improved ex vivo expansion and functional preservation of expanded HSCs. Our findings provide a rationale for the use of ASPP 049 to grow HSCs prior to hematological disease treatment.
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The methanolic extract from the dried rhizomes of Curcuma comosa cultivated in Thailand was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the ...methanolic extract, three new diarylheptanoids, diarylcomosols I–III, were isolated together with 12 known diarylheptanoids. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence. The diarylheptanoids inhibited melanogenesis, and several structural requirements of the active constituents for the inhibition were clarified. In particular, (3R)-1,7-bis(4-hydroxyphenyl)-(6E)-6-hepten-3-ol exhibited stronger inhibitory effect IC50=0.36μM without inducing cytotoxicity. The biological effect was much stronger than that of a reference compound, arbutin IC50=174μM. We conclude that diarylheptanoid analogs are promising therapeutic agents for the treatment of skin disorders.
Novel series of cyclic C
-curcuminoids 17a-j and 19-22 were prepared as cytotoxic agents and evaluated against human neuroblastoma (SH-SY5Y) or human grade IV astrocytoma (CCF-STTG1) cell lines in ...low (∼0.1 nM - 10 nM) concentrations. Among the tested 21 derivatives, 16 displayed potent antiproliferative activity with IC
values in the low nanomolar to picomolar range (IC
= 7.483-0.139 nM). Highly active compounds like N-monocarboxylic derivative 19b with IC
= 0.139 nM value against neuroblastoma and N-alkyl substituted 11 with IC
= 0.257 nM against astrocytoma proved some degree of selectivity toward non-cancerous astrocytes and kidney cells. This potent anticancer activity did not show a strong correlation with experimental logP
values, but the most potent antiproliferative molecules 11-13 and 19-22 are belonging to discrete subgroups of the cyclic C
-curcuminoids. Compounds 12, 17c and 19b were subjected to blood-brain barrier (BBB) penetration studies, too. The BBB was revealed to be permeable for all of them but, as the apparent permeability coefficient (P
) values mirrored, in different ratios. Lower toxicity of 12, 17c and 19b was observed toward primary rat brain endothelial cells of the BBB model, which means they remained undamaged under 10 µM concentrations. Penetration depends, at least in part, on albumin binding of 12, 17c and 19b and the presence of monocarboxylic acid transporters in the case of 19b. Permeation through the BBB and albumin binding, we described here, is the first example of cyclic C
-curcuminoids as to our knowledge.
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