Resveratrol, a naturally occurring stilbene, exhibits numerous beneficial health effects. Various studies have demonstrated its diverse biological actions, including anti-oxidant, anti-inflammatory, ...and anti-platelet properties, thereby supporting its potential for cardio protection, neuroprotection, and anti-cancer activity. However, a significant limitation of resveratrol is its weak bioavailability. To overcome this challenge, multiple research groups have investigated the synthesis of new resveratrol derivatives to enhance bioavailability and pharmacological activities. Nevertheless, there are limited data on the effects of resveratrol derivatives on platelet function. Therefore, the objective of this study was to synthesize resveratrol methoxy derivatives and evaluate their anti-platelet and anti-proliferative activity. Platelet-rich plasma (PRP) obtained from healthy volunteers was utilized to assess the derivatives' ability to inhibit platelet aggregation induced by platelet activating factor (PAF), adenosine diphosphate (ADP), and thrombin receptor activating peptide (TRAP). Additionally, the derivatives' anti-tumor activity was evaluated against the proliferation of PC-3 and HCT116 cells. The results revealed that some methoxy derivatives of resveratrol exhibited comparable or even superior anti-platelet activity compared to the original compound. The most potent derivative was the 4'-methoxy derivative, which demonstrated approximately 2.5 orders of magnitude higher anti-platelet activity against TRAP-induced platelet aggregation, indicating its potential as an anti-platelet agent. Concerning in silico studies, the 4'-methyl group of 4'-methoxy derivative is oriented similarly to the fluorophenyl-pyridyl group of Vorapaxar, buried in a hydrophobic cavity. In terms of their anti-tumor activity, 3-MRESV exhibited the highest potency in PC-3 cells, while 3,4'-DMRESV and TMRESV showed the greatest efficacy in HCT116 cells. In conclusion, methoxy derivatives of resveratrol possess similar or improved anti-platelet and anti-cancer effects, thereby holding potential as bioactive compounds in various pathological conditions.
Sixteen new 2-substituted quinazolines were synthesized using a straightforward methodology starting from 2-methoxybezoic acid or 3-methoxy-2-naphthoic acid. The anti-proliferative activity of the ...target compounds was evaluated against nine cancer cell lines. Additionally, all the compounds were screened for their potency and selectivity against a panel of 109 kinases and four bromodomains, using Differential Scanning Fluorimetry (DSF). Compound
bearing a 2-methoxyphenyl substitution along with a basic side chain displayed a remarkable profile against the majority of the tested cell lines.
Hydroxytyrosol and two other polyphenols of olive tree, hydroxytyrosol acetate and 3,4-dihydroxyphenylglycol, are known for a wide range of beneficial activities in human health and prevention from ...diseases. The inability to isolate high, pure amounts of these natural compounds and the difficult and laborious procedures for the synthesis of them led us to describe herein an efficient, easy, cheap, and scaling up synthetic procedure, from catechol, via microwave irradiation.
Quantitation of chromophore-free analytes is always a challenge. To this purpose, derivatization of the analyte constitutes a common strategy, leading to a product with a strong signal. In the ...current study, a novel xanthone analogue was utilized for the first time for the derivatization of pregabalin, a model analyte with a primary amine moiety that lacks a chromophore. The fact that only the xanthene-based derivative, formed after the derivatization reaction fluoresces, enables avoiding its chromatographic separation from the reagent and thus reducing the analysis time of a series of samples in 1-2 min via a plate reader. The reaction conditions were optimized via a central composite design (CCD), with fluorescence signal as the measure of the yield. The following factors that affect the derivatization reaction were chosen: (a) temperature, (b) reaction time, and (c) triethylamine solution volume used to drive the reaction to completion. After the identification of the optimal conditions, the method was validated according to ICH guidelines, using a fluorescence plate reader for signal measurement (λ
= 540, λ
= 615 nm). Finally, the newly developed high-throughput method was applied to the determination of drug content in pregabalin bulk.
Pyrano 3,4-bindol-1(9H)-ones and indolo 2,3-ccoumarins are important classes of heterocyclic compounds with versatile biological activities. Herein, we describe a straightforward and scalable ...synthesis of 3,6-dihydro-5H-pyrazolo 4′,3′:5,6pyrano 3,4-bindol-5-one, a pyrazolo-fused pyrano 3,4-bindolone, via a three step approach including Fischer-indole synthesis and intramolecular esterification. The compound is fully characterized by means of 1H and 13C NMR spectra, using direct and long-range heteronuclear correlation experiments (HMBC and HMQC).
Bone morphogenetic protein (BMP) signaling is mediated by transmembrane protein kinases that form heterotetramers consisting of type-I and type-II receptors. Upon BMP binding, the constitutively ...active type-II receptors activate specific type-I receptors by transphosphorylation, resulting in the phosphorylation of SMAD effector proteins. Drug discovery in the receptor tyrosine kinase-like (TKL) family has largely focused on type-I receptors, with few inhibitors that have been published targeting type-II receptors. BMPR2 is involved in several diseases, most notably pulmonary arterial hypertension, but also contributes to Alzheimer’s disease and cancer. Here, we report that macrocyclization of the promiscuous inhibitor 1, based on a 3-amino-1H-pyrazole hinge binding moiety, led to a selective and potent BMPR2 inhibitor 8a.
Display omitted
Several new amino-substituted acridone and xanthone derivatives have been designed and synthesized, using an efficient methodology from suitable acridone- or xanthone-carboxylic acid ...intermediates. The antiproliferative activity of the target compounds has been evaluated against four cancer cell lines, namely breast adenocarcinoma MCF-7, acute lymphocytic leukemia CCRF-CEM, and its doxorubicin-resistant variant CEM/ADR5000 and prostate cancer PC-3 cell lines. Selected derivatives have also been tested against the urinary bladder T24 and metastatic melanoma WM266-4 cancer cell lines. Two nitro substituted acridones, bearing a basic side chain as well, were endowed with a remarkable profile against the majority of the cell lines tested, with IC50 values in the low micromolar range. Both compounds cause accumulation at G0/G1 phase, induce apoptosis, and act as potent autophagy inhibitors in PC-3 cells, suggesting their further evaluation in various pathophysiological environments, conditions, and regimens.
Pyrano 3,4-bindol-1(9H)-ones and indolo 2,3-ccoumarins are important classes of heterocyclic compounds with versatile biological activities. Herein, we describe a straightforward and scalable ...synthesis of 3,6-dihydro-5H-pyrazolo 4′,3′:5,6pyrano 3,4-bindol-5-one, a pyrazolo-fused pyrano 3,4-bindolone, via a three step approach including Fischer-indole synthesis and intramolecular esterification. The compound is fully characterized by means of sup.1 H and sup.13 C NMR spectra, using direct and long-range heteronuclear correlation experiments (HMBC and HMQC).
To detect an analyte, typically at the sub-nanomolar scale, extremely sensitive analytical tools are required. Fluorescence is the spectroscopy of choice to achieve such a level due to its ...non-invasive nature and efficiency in accurately probing the sub-nanomolar concentration range. Here, we report the design, synthesis and photophysical characterization of a fluorogenic derivatization reagent with exclusive selectivity for primary amines. This xanthene-based dye owns an exacerbated fluorogenic character making the derivatized amine absorbing in yellow and emitting in the vermilion edge. In addition to being fluorogenic, this derivatization method also has the crucial advantage of being chromogenic (colorless => fuchsia). Chemical quantum calculations give an insight into the dye's molecular properties, while the development of an LC analytical method provides proof of concept regarding its application for the analysis of primary amines in a complex matrix.
MAGENTA or RED: select your 1° amine detection colorȦ .☺ Display omitted
•The identification of challenging amines in complex extracts of natural products requires more and more innovative and sensitive spectroscopic methods.•A xanthene-based derivatization reagent was engineered for the exclusive detection of primary amines.•Thanks to its chromogenic nature (colorless => magenta), the derivatization process becomes accessible to a broader audience.•The developed fluorogenic sensing (non-fluorescent => red) allows the method to reach an exquisite sensitivity level, approaching the picomolar range.
PDF
