The methanol extract of the leafy covers of Corylus avellana, source of the Italian PGI (protected geographical indication) product "Nocciola di Giffoni", afforded two new cyclic diarylheptanoids, ...giffonins T and U (2 and 3), along with two known cyclic diarylheptanoids, a quinic acid, flavonoid-, and citric acid derivatives. The structures of giffonins T and U were determined as highly hydroxylated cyclic diarylheptanoids by 1D and 2D NMR experiments. Their relative configurations were assigned by a combined quantum mechanical/NMR approach, comparing the experimental
C/
H NMR chemical shift data and the related predicted values. The absolute configurations of carpinontriol B (1) and giffonins T and U (2 and 3) were assigned by comparison of their experimental electronic circular dichroism curves with the TDDFT-predicted curves. The ability of the compounds to inhibit the lipid peroxidation induced by H
O
and H
O
/Fe
was determined by measuring the concentration of thiobarbituric acid reactive substances. Furthermore, the antimicrobial activity of the methanol extract of leafy covers of C. avellana and of the isolated compounds against the Gram-positive strains Bacillus cereus and Staphylococcus aureus and the Gram-negative strains Escherichia coli and Pseudomonas aeruginosa was evaluated. Carpinontriol B (1) and giffonin U (3) at 40 μg/disk caused the formation of zones of inhibition.
belongs to the Zingiberaceae family. In this study, two natural compounds were isolated from
, and their structures were determined using nuclear magnetic resonance. The isolated compounds were ...identified as 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-phenyl-(1
)-1-heptene (
) and
-1,7-diphenyl-5-hydroxy-1-heptene (
). Compound
showed the strongest cytotoxicity effect against HL-60 cells, while its antioxidant and anti-inflammatory properties were stronger than those of compound
. Compound
proved to be a potent antioxidant, compared to ascorbic acid. Neither compounds had any effect on red blood cell haemolysis. Furthermore, compound
significantly decreased Wilms' tumour 1 protein expression and cell proliferation in KG-1a cells. Compound
decreased the WT1 protein levels in a time- and dose- dependent manner. Compound
suppressed cell cycle at the S phase. In conclusion, compound
has a promising chemotherapeutic potential against leukaemia.
Ten hitherto unknown and ten known diarylheptanoids were isolated from the Alnus glutinosa bark and exhibited significant cytotoxic activities against NCI-H460 and NCI-H460/R cancer cell lines. ...Display omitted
•Twenty diarylheptanoids, ten new, were isolated from the bark of Alnus glutinosa.•Structural elucidation of all isolated compounds was performed by NMR, MS, UV, IR, and CD.•Two new compounds, 14 and 18, exhibited significant anti-cancer activity and selectivity.•SAR revealed high dependence of anti-cancer activity on substitution pattern of diarylheptanoids.•Diarylheptanoids 3 and 6 exhibited a potential for overcoming multi-drug resistance.
An extended study of minor diarylheptanoids from the bark of black alder has resulted in the isolation of twenty diarylheptanoids, ten of which have not previously been reported (14–18, 20–24). The structures and configurations of all compounds were elucidated by NMR, HRESIMS, UV, IR, and CD. The anti-cancer potency of twenty diarylheptanoids and four previously isolated compounds (7, 10, 12, 13) was investigated in human non-small cell lung carcinoma cell lines (sensitive and multi-drug resistant variants) as well as in normal human keratinocytes. Diarylheptanoids with a p-coumaroyl group, 14 and 18, platyphylloside (1), platyphyllonol-5-O-β-d-xylopyranoside (2), alnuside B (4) and hirsutenone (9) exhibited strong anti-cancer activity, considerably higher than diarylheptanoid curcumin, which served as a positive control. Compounds 4, 9, 14, and 18 displayed significant selectivity towards the cancer cells. Structure/activity analysis of twenty-four closely related diarylheptanoids revealed a high dependence of cytotoxic action on the presence of a carbonyl group at C-3. Substitution of a heptane chain on C-5 and a number of hydroxyl groups in the aromatic rings also emerged as a significant structural feature that influenced their cytotoxic potential.
In continuation of our effort to improve the physiological stability and the antibacterial activity of curcuminoids against drug-resistant bacteria, a series of novel monocarbonyl curcuminoids were ...synthesized and screened for antibacterial activity against S. aureus and E. coli strains. These curcuminoids showed potent antibacterial activity against both methicillin-sensitive and methicillin-resistant strains of S. aureus with MIC values 2–8 and 4–16 μg/mL, respectively. They also exhibited moderate potency against E. coli strains. The four most active curcuminoids (7d, 7i, 7m, and 7p) were on further investigation found to be very stable under physiological conditions, non-hemolytic, and non-toxic toward mammalian cells up to 150 μg/mL concentration. Mechanistic studies revealed that these curcuminoids displayed potent bactericidal activity by targeting cell membranes. Further, in an ex vivo mammalian co-culture infection model study, remarkably, the curcuminoids 7i and 7p were able to clear the internalized bacteria in mammalian cells and the activity was found to be superior to conventional antibiotics such as vancomycin and linezolid. Therefore, the present study affords us water-soluble, stable, non-toxic curcuminoids that may serve as lead molecules for development as antibacterial agents against MRSA infections.
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•A series of novel, water-soluble, and physiologically stable curcuminoids was synthesized.•Curcuminoids were active against both S. aureus and E. coli bacterial strains.•Most active compounds (7d, 7i, 7m, and 7p) were found to be non-hemolytic and non-toxic.•The study revealed that these compounds target bacterial cell membranes.•Exvivo study of 7i and 7p displayed the superior antibiotic activity than conventional drugs.
Propolis is commercialized in Chile as an antimicrobial agent. It is obtained mainly from central and southern Chile, but is used for the same purposes regardless of its origin. To compare the ...antimicrobial effect, the total phenolic (TP), the total flavonoid (TF) content and the phenolic composition, 19 samples were collected in the main production centers in the Región del Maule, Chile. Samples were extracted with MeOH and assessed for antimicrobial activity against Gram (+) and Gram (-) bacteria. TP and TF content, antioxidant activity by the DPPH, FRAP and TEAC methods were also determined. Sample composition was assessed by HPLD-DAD-ESI-MS/MS. Differential compounds in the samples were isolated and characterized. The antimicrobial effect of the samples showed MICs ranging from 31.5 to > 1000 µg/mL. Propolis from the central valley was more effective as antibacterial than those from the coastal area or Andean slopes. The samples considered of interest (MIC ≤ 62.5 µg/mL) showed effect on Escherichia coli, Pseudomonas sp., Yersinia enterocolitica and Salmonella enteritidis. Two new diarylheptanoids, a diterpene, the flavonoids pinocembrin and chrysin were isolated and elucidated by spectroscopic and spectrometric means. Some 29 compounds were dereplicated by HPLC-MS and tentatively identified, including nine flavones/flavonol derivatives, one flavanone, eight dihydroflavonols and nine phenyl-propanoids. Propolis from the Región del Maule showed large variation in antimicrobial effect, antioxidant activity and composition. So far the presence of diarylheptanoids in samples from the coastal area of central Chile can be considered as a marker of a new type of propolis.
Two undescribed diarylheptanoids, 3-(R)-acetyl-1-(3′,4′-dihydroxyphenyl)-7-(4′′-hydroxy-3′′ -methoxyphenyl)-heptane (1) and 11-Hydroxy-1,17-epoxy-7-(2-hydroxylphenyl)-13-(16-methoxyphenyl)-heptane ...(2) together with known compounds, namely, 11-Oxo-1,17-epoxy-7-(2-hydroxylphenyl)-13-(16-methoxyphenyl)-heptane (3) 3,4,5-Trihydroxytetralone (4) 4,8- Dihydroxytetralone (5), 4,5-Dihydroxytetralone (6), 5,8-Dihydroxy-3-methoxytetralone (7) were isolated from ethyl acetate extract of the green husk of Carya illinoinensis. The structures of compounds were established on the basis of IR,
1
H NMR,
13
C NMR, DEPT, HSQC, HMBC, COSY spectroscopic and ESI-MS analysis. The isolated compounds were evaluated for AChE (acetylcholinesterase inhibition) and observed that compound 5 was potent inhibitor with IC
50
of 101.48 ± 4.00 µg/mL.
Pancreatic cancer is one of the leading causes of cancer, and it has the lowest 5-year survival rates. It is necessary to develop more potent anti-pancreatic cancer drugs to overcome the fast ...metastasis and resistance to surgery, radiotherapy, chemotherapy, and combinations of these. We have identified several diarylheptanoids as anti-pancreatic cancer agents from
Alpinia officinarum
(lesser galangal) and
Alnus japonica
. These diarylheptanoids suppressed cell proliferation and induced the cell cycle arrest of pancreatic cancer cells (PANC-1). Among them, the most potent compounds
1
and
7
inhibited the shh-Gli-FoxM1 pathway and their target gene expression in PANC-1 cells. Furthermore, they suppressed the expression of the cell cycle associated genes that were rescued by the overexpression of exogenous FoxM1. Taken together, (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (
1
) from
Alpinia officinarum
(lesser galangal) and platyphyllenone (
7
) from
Alnus japonica
inhibit PANC-1 cell proliferation by suppressing the shh-Gli-FoxM1 pathway, and they can be potential candidates for anti-pancreatic cancer drug development.
The lack of effective pharmacological treatments for acute kidney injury (AKI) remains a significant public health problem. Given the involvement of apoptosis and regulated necrosis in the initiation ...and progression of AKI, the inhibition of cell death may contribute to AKI prevention/recovery. Curcuminoids are a family of plant polyphenols that exhibit attractive biological properties that make them potentially suitable for AKI treatment. Now, in cultured tubular cells, we demonstrated that a crosslinked self-assembled star-shaped polyglutamate (PGA) conjugate of bisdemethoxycurcumin (St-PGA-CL-BDMC) inhibits apoptosis and necroptosis induced by Tweak/TNFα/IFNγ alone or concomitant to caspase inhibition. St-PGA-CL-BDMC also reduced NF-κB activation and subsequent gene transcription. In vivo, St-PGA-CL-BDMC prevented renal cell loss and preserved renal function in mice with folic acid-induced AKI. Mechanistically, St-PGA-CL-BDMC inhibited AKI-induced apoptosis and expression of ferroptosis markers and also decreased the kidney expression of genes involved in tubular damage and inflammation, while preserving the kidney expression of the protective factor, Klotho. Thus, due to renal accumulation and attractive pharmacological properties, the application of PGA-based therapeutics may improve nephroprotective properties of current AKI treatments.
Breast cancer consists of heterogenic subpopulations, which determine the prognosis and response to chemotherapy. Among these subpopulations, a very limited number of cancer cells are particularly ...problematic. These cells, known as breast cancer stem cells (BCSCs), are thought responsible for metastasis and recurrence. They are thus major contributor to the unfavorable outcomes seen for many breast cancer patients. BCSCs are more prevalent in the hypoxic niche. This is an oxygen-deprived environment that is considered crucial to their proliferation, stemness, and self-renewal but also one that makes BCSCs highly refractory to traditional chemotherapeutic regimens. Here we report a small molecule construct,
, that allows the therapeutic targeting of BCSCs and which is effective in normally refractory hypoxic tumor environments. A related system,
, has been developed that permits CSC imaging. Several design elements are incorporated into
, including the CAIX inhibitor acetazolamide (Az) to promote localization in MDA-MB-231 CSCs, a dimethylnitrothiophene subunit as a hypoxia trigger, and a 3,4-difluorobenzylidene curcumin (CDF) as a readily released therapeutic payload. This allows
to serve as a hypoxia-liable molecular platform that targets BCSCs selectively which decreases CSC migration, retards tumor growth, and lowers tumorigenesis rates as evidenced by a combination of in vitro and in vivo studies. To the best of our knowledge, this is the first time a CSC-targeting small molecule has been shown to prevent tumorigenesis in an animal model.
In efforts to develop effective anticancer therapeutics with greater selectivity toward cancerous cell and reduced side-effects, such as emetic effects due to detrimental action of the drug toward ...the intestinal flora, a series of linear diarylheptanoids (LDHs) were designed and synthesized in 7 steps with good-to-moderate yields. All synthesized compounds were evaluated for their antibacterial, antiproliferative, and topoisomerase-I and -IIα inhibitory activity. Overall, all compounds showed little to no activity against the bacterial strains tested. Most of the synthesized compounds showed good antiproliferative activity against human breast cancer cell lines (T47D); specifically, the IC
50
values of compounds
6a
,
6d
,
7j
, and
7e
were 0.09, 0.64, 0.67, and 0.99 μM, respectively. Among the tested compounds,
7b
inhibited topo-I by 9.3% (camptothecin 68.8%),
7e
and
7h
inhibited topo-IIα by 38.4 and 47.4% (etoposide 76.9%), respectively, at the concentration of 100 μM. These results suggest that a set of promising anticancer agents can be obtained by reducing inhibitory actions on different microbes to provide enhanced selectivity against cancerous cells.
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