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Curcuminoids, polyphenol compounds in turmeric, possess several pharmacological properties including antioxidant, iron-chelating, and anti-inflammatory activities. Effects of curcuminoids in thalassemia patients have been explored in a limited number of studies using different doses of curcuminoids. The present study aims to evaluate the effects of 24-week curcuminoids supplementation at the dosage of 500 and 1000 mg/day on iron overload, oxidative stress, hypercoagulability, and inflammation in non-transfused β-thalassemia/Hb E patients. In general, both curcuminoids dosages significantly lowered the levels of oxidative stress, hypercoagulability, and inflammatory markers in the patients. In contrast, reductions in iron parameter levels were more remarkable in the 1000 mg/day group. Subgroup analysis revealed that a marker of hypercoagulability was significantly decreased only in patients with baseline ferritin ≤ 1000 ng/ml independently of curcuminoids dosage. Moreover, the alleviation of iron loading parameters was more remarkable in patients with baseline ferritin > 1000 ng/ml who receive 1000 mg/day curcuminoids. On the other hand, the responses of oxidative stress markers were higher with 500 mg/day curcuminoids regardless of baseline ferritin levels. Our study suggests that baseline ferritin levels should be considered in the supplementation of curcuminoids and the appropriate curcuminoids dosage might differ according to the required therapeutic effect. Thai Clinical Trials Registry (TCTR): TCTR20200731003; July 31, 2020 “retrospectively registered”

Curcumin and curcuminoids have been discussed frequently due to their promising functional groups (such as scaffolds of α,β-unsaturated β-diketone, α,β-unsaturated ketone and β′-hydroxy-α,β-unsaturated ketone connected with aromatic rings on both sides) that play an important role in various bioactivities, including antioxidant, anti-inflammatory, anti-proliferation and anticancer activity. A series of novel curcuminoid derivatives (a total of 55 new compounds) and three reference compounds were synthesized with good yields using three-step organic synthesis. The anti-proliferative activities of curcumin derivatives were examined for six human cancer cell lines: HeLaS3, KBvin, MCF-7, HepG2, NCI-H460 and NCI-H460/MX20. Compared to the IC50 values of all the synthesized derivatives, most α,β-unsaturated ketones displayed potent anti-proliferative effects against all six human cancer cell lines, whereas β′-hydroxy-α,β-unsaturated ketones and α,β-unsaturated β-diketones presented moderate anti-proliferative effects. Two potent curcuminoid derivatives were found among all the novel derivatives and reference compounds: (E)-5-hydroxy-7-phenyl-1-(3,4,5-trimethoxyphenyl)hept-1-en-3-one (compound 3) and (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a). These were selected for further analysis after the evaluation of their anti-proliferative effects against all human cancer cell lines. The results of apoptosis assays revealed that the number of dead cells was increased in early apoptosis and late apoptosis, while cell proliferation was also decreased after applying various concentrations of (E)-5-hydroxy-7-phenyl-1-(3,4,5-trimethoxyphenyl)hept-1-en-3-one (compound 3) and (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a) to MCF-7 and HpeG2 cancer cells. Analysis of the gene expression arrays showed that three genes (GADD45B, SESN2 and BBC3) were correlated with the p53 pathway. From the quantitative PCR analysis, it was seen that (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a) effectively induced the up-regulated expression of GADD45B, leading to the suppression of MCF-7 cancer cell formation and cell death. Molecular docking analysis was used to predict and sketch the interactions of the GADD45B-α,β-unsaturated ketone complex for help in drug design.

Neurodegenerative diseases represent a set of pathologies characterized by an irreversible and progressive, and a loss of neuronal cells in specific areas of the brain. Oxidative phosphorylation is a source of energy production by which many cells, such as the neuronal cells, meet their energy needs. Dysregulations of oxidative phosphorylation induce oxidative stress, which plays a key role in the onset of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). To date, for most neurodegenerative diseases, there are no resolute treatments, but only interventions capable of alleviating the symptoms or slowing the course of the disease. Therefore, effective neuroprotection strategies are needed. In recent years, natural products, such as curcuminoids, have been intensively explored and studied for their therapeutic potentials in several neurodegenerative diseases. Curcuminoids are, nutraceutical compouns, that owen several therapeutic properties such as anti-oxidant, anti-inflammatory and neuroprotective effects. In this context, the aim of this review was to provide an overview of preclinical and clinical evidence aimed to illustrate the antioxidant effects of curcuminoids in neurodegenerative diseases. Promising results from preclinical studies encourage the use of curcuminoids for neurodegeneration prevention and treatment.

LIMK1 has been demonstrated to be highly correlated with the progression and overall survival rates of colorectal cancer (CRC) patients. In this study, a series of diarylheptanoid scaffold derivatives were intentionally designed and synthesised to evaluate their potential as LIMK1 inhibitors. Among these compounds, compounds and exhibited LIMK1 inhibitory activity with IC values of 0.94 and 0.57 µM, respectively. We also disclosed the structure-activity relationship of the resulting compounds that exhibited LIMK1 inhibition. Catechol-containing diarylheptanoid was identified as a promising scaffold for LIMK1 inhibitors. Notably, compound demonstrated selectivity in inhibiting the tyrosine kinase-like family and exhibited potent inhibition of CRC cells. Moreover, compound induced an increase in the S phase and a decrease in the G0/G1 phase in a dose-dependent manner, indicating apoptosis induction. These findings establish compound as a lead compound for the further development of anti-CRC agents.

Many linear diarylpentanoids and diarylheptanoids contain a β-hydroxy ketone or 1,3-diol functionality as the structural motif. Reported herein is the asymmetric synthesis of (S)-daphneolone, (S)-dihydroyashabushiketol, and formal synthesis of (3S,5S)-yashabushidiol B as represented examples, employing readily accessible (3S)-hydroxy-5-phenylpentanoic acid. The (3S)-hydroxy-5-phenylpentanoic acid was conveniently prepared by the aldol addition of (R)-acetyloxazolidinone with 3-phenylpropanal affording two diastereomers which were cleanly separated by silica gel column chromatography, followed by the removal of Evans auxiliary of (3′R,4S)-imide. Then, the (S)-acid was converted to Weinreb amide as a privileged acylating agent. Three natural products with the uppermost optical purity were prepared by the treatment of organolithium or organomagnesium reagents, respectively, to the Weinreb amide used in common. We believe that this strategy provides a rapid and convergent method for constructing these classes of molecules of interest.

Curcumin (CUR) is the primary metabolite isolated from the Curcuma longa L. rhizome. Most synthetic and biological studies have focused mainly on the curcumin molecule due to its essential biological activity as an antioxidant, anti-cancer, and anti-Alzheimer’s disease agent. However, the natural extract of turmeric also contains two essential curcuminoids (demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)), which altogether comprise the so-called C-3 complex. They are present in commercial compositions for treating biliary or digestive ailments. The vegetal rhizome’s extraction typically leads to a mixture of the three main curcuminoids, CUR, DMC, and BDMC, in variable proportions, and each of these metabolites has reported specific synthetic routes. Herein, we have performed the synthesis and isolation of the three major curcuminoids using the method called scrambling of aldehydes followed by aldol di-condensation reactions. A density functional theory (DFT) approach supported the experimental results by inspecting the predicted energies for the aldol condensation. Thus, the di-condensation reaction is substantially favoured (ΔG° = −2685.9 kJ/mol) over the mono-condensation reaction (ΔG° = −1393.753 kJ/mol). Our approach allows us to mimic closely the proportions of these curcuminoids found in extracts from natural sources that follow the order CUR > DMC > BDMC, respectively. The proportion of aldehydes can be modified in the scrambling reaction with an adequate mixture of aldehydes to render the order DMC > CUR > BDMC. This is an advantageous way to increase the amount of the unsymmetric DMC metabolite.

The search for bioactive compounds against chronic diseases such as cancer and diabetes includes curcuminoids as promising scaffolds. Here, we report the synthesis of a family of curcuminoid analogue compounds with an extended unsaturated central chain, as follows: difluoroboron complex 1, the enolised curcuminoid 2, and its homoleptic copper complex 3, in moderate to good yields (68–90%). Additionally, their β-cyclodextrin (BCD) association complexes, 4 and 5, were prepared through a mechanochemical method and characterised by spectroscopic techniques. Complete 1H and 13C NMR assignments and NOESY correlations revealed unique solvent effects on the conformational disposition of compound 2, while the copper complex 3 displayed the highest extinction coefficient (1.20 × 105 M−1·cm−1). Furthermore, the authentication of the polymorph of 1 and the new crystal structures of 2 and 3, determined by single-crystal X-ray analysis, were highlighted. Although the copper complex 3 initially exhibited the lowest a-glucosidase inhibitory activity (IC50 > 100 µM), it showed a significant increase (IC50 = 36.27 µM) upon association with BCD, reaching values comparable to the free ligand (IC50 = 45.63 µM). Compounds 1–5 were non-toxic to healthy cells (COS-7), but compound 5 stands out as a promising candidate against this metabolic condition.

Curcuma comosa belongs to the Zingiberaceae family. In this study, two natural compounds were isolated from C. comosa, and their structures were determined using nuclear magnetic resonance. The isolated compounds were identified as 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (1) and trans-1,7-diphenyl-5-hydroxy-1-heptene (2). Compound 1 showed the strongest cytotoxicity effect against HL-60 cells, while its antioxidant and anti-inflammatory properties were stronger than those of compound 2. Compound 1 proved to be a potent antioxidant, compared to ascorbic acid. Neither compounds had any effect on red blood cell haemolysis. Furthermore, compound 1 significantly decreased Wilms’ tumour 1 protein expression and cell proliferation in KG-1a cells. Compound 1 decreased the WT1 protein levels in a time- and dose- dependent manner. Compound 1 suppressed cell cycle at the S phase. In conclusion, compound 1 has a promising chemotherapeutic potential against leukaemia.

Alnustone, a nonphenolic diarylheptanoid, first isolated from Alnus pendula (Betulaceae), has recently received a great deal of attention due to its various beneficial pharmacological effects. However, its pharmacokinetic profile in vivo remains unclear. The purpose of this study is to establish a fast and sensitive quantification method of alnustone using liquid chromatography tandem mass spectrometry (LC-MS/MS) and evaluate the pharmacokinetic and tissue distribution profiles of alnustone in rats. The sample was precipitated with acetonitrile with 0.5% formic acid and separated on BEH C18 Column. The mobile phase was composed of 0.1% formic acid in water and methanol at a flow rate of 0.3 mL/min. Alnustone and the internal standard (caffeine) were quantitatively monitored with precursor-to-product ion transitions of m/z 262.9→105.2 and m/z 195.2→138.0, respectively. The calibration curve for alnustone was linear from 1 to 2000 ng/mL. The intra- and inter-day assay precision (RSD) ranged from 1.1–9.0 % to 3.3–8.6%, respectively and the intra- and inter-day assay accuracy (RE) was between −8.2–9.7% and −10.3–9.9%, respectively. The validated method was successfully applied to the pharmacokinetic studies of alnustone in rats. After single-dose intravenous administration of alnustone (5 mg/kg), the mean peak plasma concentration (Cmax) value was 7066.36 ± 820.62 ng/mL, and the mean area under the concentration-time curve (AUC0–t) value was 6009.79 ± 567.30 ng/mL∙h. Our results demonstrated that the residence time of alnustone in vivo was not long and it eliminated quickly from the rat plasma. Meanwhile, the drug is mainly distributed in tissues with large blood flow, and the lung and liver might be the target organs for alnustone efficacy. The study will provide information for further application of alnustone.

Six biobased ionic liquids were prepared from saturated fatty acids (octanoic, decanoic and dodecanoic acids) and choline with yields up to 90% following procedures respecting green chemistry principles. These ionic liquids were fully characterized (NMR, IR, elemental analysis, viscosimetry and TGA) and used as extraction solvents for bioactive compounds (curcuminoids and carvacrol) using classical conditions, and the ionic liquids were able to be recovered after five runs without loss of activity. The ionic liquid containing a C12 carbon chain was the best extracting solvent, extracting 95% of the total curcuminoids contained in turmeric and 69% of the total carvacrol contained in oregano, which are higher yields compared to the extraction procedures described in the literature. As C12 ionic liquids were more cytotoxic than C8 ones, the biological activity of the curcuminoids extracted with C8 ionic liquids was evaluated on a MIAPaCa-2, a pancreatic adenocarcinoma cell line for which antitumor activity of curcuminoids had previously been reported. Compared to the cytotoxicity of the commercially available extract, the cytotoxic activity of the extracts was slightly weaker.