Synthesis and Anticancer Activity of Novel Derivatives of α,ß-Unsaturated Ketones Based on Oleanolic Acid: in Vitro and in Silico Studies against Prostate Cancer Cells.

Herein, new derivatives of α,ß-unsaturated ketones based on oleanolic acid (4 a-i) were designed, synthesized, characterized, and tested against human prostate cancer (PC3). According to the in vitro cytotoxic study, title compounds (4 a-i) showed significantly lower toxicity toward healthy cells (HUVEC) in comparison with the reference drug doxorubicin. The compounds with the lowest IC50 values on PC3 cell lines were 4 b (7.785 µM), 4 c (8.869 µM), and 4 e (8.765 µM). The results of the ADME calculations showed that the drug-likeness parameters were within the defined ranges according to Lipinski's and Jorgensen's rules. For the most potent compounds 4 b, 4 c, and 4 e, a molecular docking analysis using the induced fit docking (IFD) protocol was performed against three protein targets (PARP, PI3K, and mTOR). Based on the IFD scores, compound 4 b had the highest calculated affinity for PARP1, while compound 4 c had higher affinities for mTOR and PI3K. The MM-GBSA calculations showed that the most potent compounds had high binding affinities and formed stable complexes with the protein targets. Finally, a 50 ns molecular dynamics simulation was performed to study the behavior of protein target complexes under in silico physiological conditions.

New porphyrins: synthesis, characterization, and computational studies.

New trans-A2B2-porphyrins substituted at phenyl positions were synthesized from 4-methylphthalic acid as a starting material through sequential multistep reactions. These macrocycles were characterized by 1H NMR, 13C NMR, 19F NMR, 1H-1H COSY NMR, and MALDI-TOF mass spectrometry. Computational studies were performed on the porphyrins to investigate various factors such as structural features, electronic energy, energy gaps, and aromaticity. Energy band gap values of these compounds especially N-hydroxyphthalimide-functionalized porphyrins were small that makes them as good candidates for solar cell systems and photocatalysis. Relationships between electronic energies and aromaticity of the compounds were then investigated. The data indicated that the aromaticity features at the center of two series of these compounds (fluorinated and non-fluorinated porphyrins) were in the opposite manner.

A hybrid material composed of an amino-functionalized zirconium-based metal-organic framework and a urea-based porous organic polymer as an efficient sorbent for extraction of uranium(VI).

An amino-functionalized zirconium metal-organic framework was composed with a 3D urea-based porous organic polymer to give a hybrid material termed UiO-66-NH2/urea-POP. The material was characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction, scanning electron microscopy, and Brunauer-Emmett-Teller surface area measurements. It is shown to be a viable sorbent for solid-phase extraction of uranium from water samples. Parameters such as the pH value of the sample, amount of adsorbent, type and volume of eluent, adsorption and desorption time, and sample volume were optimized. Uranyl ion was quantified by using UV-vis spectrophotometry by using 1-(2-pyridyl-azo)-2-naphthol as the indicator. Figures of merits include (a) a maximum sorption capacity of 278 mg g-1; (b) a detection limit of 0.6 µg L-1; and (c) intra-day and inter-day precisions (for n = 5 at a concentration of 100 µg L-1) of 4.8 and 1.9%, respectively. The sorbent can be recycled, and no significant change was observed in the capacity and repeatability of the sorbent after seven extractions. The high surface area, metal-binding sites, and stability of the sorbent makes it a most viable tool for efficient and fast extraction and removal of uranium. Graphical abstract Schematic of a new porous hybrid solid, referred to as UiO-66-NH2/urea-POP. It combines a zirconium-based metal-organic framework and a urea-based porous organic polymer. It is shown to be a highly efficient sorbent for solid-phase extraction of uranium(VI) prior to its spectrophotometric determination.

Maghemite nanoparticle-decorated hollow fiber electromembrane extraction combined with dispersive liquid-liquid microextraction for determination of thymol from Carum copticum.

BACKGROUND: A novel technique using maghemite nanoparticle-decorated hollow fibers to assist electromembrane extraction is proposed. Electromembrane extraction combined with dispersive liquid-liquid microextraction (EME-DLLME) was applied for the extraction of thymol from Carum copticum, followed by gas chromatography with flame ionization detection (GC-FID). RESULTS: The use of maghemite nanoparticle-decorated hollow fibers was found to improve the extraction efficiency of thymol significantly. Important operational parameters, including pH of acceptor phase, extraction time, voltage and temperature, were investigated and optimized. At the optimal conditions, linearity in the range 4-1800 µg L-1 with a determination coefficient of 0.9996 was obtained. The limit of detection was 0.11 µg L-1 (S/N = 3) and the pre-concentration factor was 200. The intra- and inter-day precision was 5.9 and 2.2% respectively. The intra- and inter-day accuracy was higher than 93.6%. CONCLUSION: The results indicated that EME-DLLME/GC-FID is a useful technique for the extraction and determination of thymol in C copticum. © 2016 Society of Chemical Industry.

Application of response surface methodology in enzymatic synthesis: a review.

There are very chemical reactions with very slow rates which can be catalyzed by enzymes. These biocatalysts need to moderate conditions for their catalytic activity and are stable in low temperature (between 15-50°C), average pH (5-10) and aqueous media. One of important things in enzymatic synthesis which has been recently noticed is the yield of reactions. Nowadays wide application of response surface methodology (RSM) was observed in organic chemistry. In one-variable-at-a-time technique only one parameter is changed and other parameters are kept at a constant level. It does not study the interactive effects among the variables, and does not illustrate the complete effects of the parameters on the process. Increasing the yield of product without increase in casts is carried out by modeling and optimization of reaction variables through statistical techniques such as RSM. In this paper, we reviewed some articles that used the RSM for optimization in the enzymatic synthesis.

Machine learning-aided enhancement of white tea extraction efficiency using hybridized GMDH models in microwave-assisted extraction.

White tea is valuable for having a high antioxidant content, which is considered to possess numerous beneficial effects on health. This study investigated the application of microwave-assisted extraction (MAE) for the extraction of total phenolic compounds from white tea. The experimental setup included four independent variables: microwave power (ranging from 100 to 300 W), extraction time (ranging from 10 to 40 min), temperature (ranging from 35 to 50 °C), and the ratio of food to solvent (ranging from 0.25 to 0.5 g/10 mL). The responses that were evaluated were IC50 (ppm) and total phenolic content (mg/g). The experimental design consisted of thirty runs conducted within the MAE system. The group method of data handling (GMDH) models were used to predict important efficiency measures (IC50 and total phenol content) in the extraction process. The models were assessed based on their ability to capture the relationships between input conditions and efficiency outputs. Three GMDH variants were compared: baseline GMDH, GMDH optimized with a genetic algorithm (GMDH-GA), and GMDH optimized with a harmony search algorithm (GMDH-HS). While all models achieved high predictive ability on a test set, GMDH-HS emerged as the superior performer. It achieved near-perfect agreement with observations (d-index > 0.998), minimal errors (NRMSE < 0.02), and effectively captured data variance (NSE > 0.99) for both outputs. Correlation diagrams and Taylor diagrams confirmed the superior performance of GMDH-HS in terms of linearity, correlation, and error minimization. This study demonstrates the effectiveness of hybridizing GMDH with a harmony search algorithm for complex modeling tasks, paving the way for improved efficiency and yield optimization in extraction processes.

Anticancer activity of 3-O-acylated betulinic acid derivatives obtained by enzymatic synthesis.

An easy and efficient strategy to prepare betulinic acid esters with various anhydrides was used by the enzymatic synthesis method. It involves lipase-catalyzed acylation of betulinic acid with anhydrides as acylating agents in organic solvent. Lipase from Candida antarctica immobilized on an acrylic resin (Novozym 435) was employed as a biocatalyst. Several 3-O-acyl-betulinic acid derivatives were successfully obtained by this procedure. The anticancer activity of betulinic acid and its 3-O-acylated derivatives were then evaluated in vitro against human lung carcinoma (A549) and human ovarian (CAOV3) cancer cell lines. 3-O-glutaryl-betulinic acid, 3-O-acetyl-betulinic acid, and 3-O-succinyl-betulinic acid showed IC(50)<10 microg/ml against A549 cancer cell line tested and showed better cytotoxicity than betulinic acid. In an ovarian cancer cell line, all betulinic acid derivatives prepared showed weaker cytotoxicity than betulinic acid.

A Pyridyltriazol Functionalized Zirconium Metal-Organic Framework for Selective and Highly Efficient Adsorption of Palladium.

This work reports the synthesis of pyridyltriazol-functionalized UiO-66 (UiO stands for University of Oslo), namely, UiO-66-Pyta, from UiO-66-NH2 through three postsynthetic modification (PSM) steps. The good performance of the material derives from the observation that partial formylation (∼21% of -NHCHO groups) of H2BDC-NH2 by DMF, as persistent impurity, takes place during the synthesis of the UiO-66-NH2. Thus, to enhance material performance, first, the as-synthesized UiO-66-NH2 was deformylated to give pure UiO-66-NH2. Subsequently, the pure UiO-66-NH2 was converted to UiO-66-N3 with a nearly complete conversion (∼95%). Finally, the azide-alkyne[3+2]-cycloaddition reaction of 2-ethynylpyridine with the UiO-66-N3 gave the UiO-66-Pyta. The porous MOF was then applied for the solid-phase extraction of palladium ions from an aqueous medium. Affecting parameters on extraction efficiency of Pd(II) ions were also investigated and optimized. Interestingly, UiO-66-Pyta exhibited selective and superior adsorption capacity for Pd(II) with a maximum sorption capacity of 294.1 mg g-1 at acidic pH (4.5). The limit of detection (LOD) was found to be 1.9 µg L-1. The estimated intra- and interday precisions are 3.6 and 1.7%, respectively. Moreover, the adsorbent was regenerated and reused for five cycles without any significant change in the capacity and repeatability. The adsorption mechanism was described based on various techniques such as FT-IR, PXRD, SEM/EDS, ICP-AES, and XPS analyses as well as density functional theory (DFT) calculations. Notably, as a case study, the obtained UiO-66-Pyta after palladium adsorption, UiO-66-Pyta-Pd, was used as an efficient catalyst for the Suzuki-Miyaura cross-coupling reaction.

Iron species supported on a mesoporous zirconium metal-organic framework for visible light driven synthesis of quinazolin-4(3H)-ones through one-pot three-step tandem reaction.

A bioinspired iron(III)porphyrinic Zr-MOF, PCN-222(Fe), was modified by post-synthetic cluster metalation with iron(III) chloride, as a cheap, earth-abundant, and environmentally friendly metal precursor, towards formation a new multifunctional MOF, namely Fe@PCN-222(Fe). The MOF consists of bimetallic (Zr-oxo-Fe) nodes linked by Fe(III)porphyrin struts. The cluster metalation and pre-activation treatment of PCN-222(Fe) were performed cooperatively using the FeCl3. The respective MOF was characterized through various techniques, such as FT-IR, PXRD, ICP-AES, BET surface area, SEM, UV-Vis DRS, TGA/DSC, PL, and XPS analyses. The solid showed catalytic activity for one-pot tandem synthesis of quinazolin-4(3H)-ones from alcohols and 2-aminobenzamide through a three-consecutive-step reaction (oxidation-cyclization-oxidation) under visible light irradiation using air or oxygen without adding any additive. In addition, its catalytic performance was superior to that of the bare PCN-222(Fe) and the corresponding homogeneous catalysts. The experiments indicate that the solid MOF acts as both a photoredox and Lewis acid catalyst. Hot-filtration and Fe-leaching tests as well as reusability experiments confirm that the nominal MOF acts as an efficient reusable heterogeneous catalyst for at least three runs without significant decrease in its activity. This work demonstrates the potential of using MOFs as supports for single-site metal species towards preparation of multifunctional MOFs for modern organic transformations combining photocatalysis and catalysis.

The role of acetoacetate in Amadori product formation of human serum albumin.

Amadori product is an important and stable intermediate, which is produced during glycation process. It is a marker of hyperglycemia in diabetes mellitus, and its accumulation in the body contributes to microvascular complication of diabetes including diabetic nephropathy and retinopathy. In this study, the effect of acetoacetate on the formation of Amadori products and biophysical properties of human serum albumin (HSA), after incubation with glucose, was investigated using various methods. These included circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy, and UV-visible and fluorescence spectroscopy. Our results indicated that the production of Amadori products in HSA incubated with glucose (GHSA) was increased in the presence of acetoacetate. We also detected alterations in the secondary and tertiary structure of GHSA, which was increased in the presence of acetoacetate. These changes were attributed to the formation of covalent bonds between the carbonyl group of acetoacetate and the nucleophilic groups (lysine residues) of HSA. Thus, acetoacetate can enhance the production of Amadori products through formation of covalent bonds with biomaterials.

Acetoacetate promotes the formation of fluorescent advanced glycation end products (AGEs).

Acetoacetate (AA) is an important ketone body, which produces reactive oxygen species (ROS). Advanced glycation end products (AGEs) are defined as final products of glycation process whose production is influenced by the levels of ROS. The accumulation of AGEs in the body contributes to pathogenesis of many diseases including complications of diabetes, and Alzheimer's and Parkinson's disease. Here, we evaluated the impact of AA on production of AGEs upon incubation of human serum albumin (HSA) with glucose. The effect of AA on the AGEs formation of HSA was studied under physiological conditions after incubation with glucose for 35 days. The physical techniques including circular dichroism (CD) and fluorescence spectroscopy were used to assess the impact of AA on formation and structural changes of glycated HSA (GHSA). Our results indicated that the secondary and tertiary structural changes of GHSA were increased in the presence of AA. The fluorescence intensity measurements of AGEs also showed an increase in AGEs formation. Acetoacetate has an activator effect in formation of AGEs through ROS production. The presence of AA may result in enhanced glycation in the presence of glucose and severity of complications associated with accumulation of AGEs.

Mechanism and behavior of silver nanoparticles in aqueous medium as adsorbent.

In recent years there has been a rising interest in the application of nanomaterial such as silver nanoparticles (AgNps) in many areas of scientific research. The most active areas of investigation are related to the study and application of optical, biomedical, and newly applied adsorption properties of AgNps. The recent evaluation of adsorptive properties of AgNPs has added new areas to their wide range of applications in analytical separations and pre-concentrating steps. They have also been used for removal of several environmental organic pollutants and uptake of heavy metals. The main objective of this review is to describe the characteristics, mechanisms, and behavior of AgNPs as adsorbent in aquatic systems and sample solutions.