Phenolics from Chilean Bee Bread Exhibit Antioxidant and Antibacterial Properties: The First Prospective Study

Posted on 13 September 2023 by

Abstract

Bee bread (BB) is a beehive product generated upon fermentation of pollen combined with flower nectar and glandular secretions. The potential application of BB is related to its nutritional and functional components, including phenolic compounds. This is the first prospective study on palynological parameters, phenolics, antioxidant, and antibacterial activity of Chilean bee bread in vitro. The tested material exhibited high levels of phenolics (1340±186 mg GAE/100 g BB) and showed antioxidant capacity as determined by the FRAP (51±2 μmol Trolox equivalent/g BB) and ORAC-FL (643±64 μmol Trolox equivalent/g BB) and antibacterial activity against Streptococcus pyogenes. Furthermore, the phenolic acids and flavonoids was determined using liquid chromatography-mass spectrometry, and the concentration was determined using liquid chromatography with diode array detection. Kaempferol, quercetin, ferulic acid, and rutin were the main phenolics found. This study demonstrates the bioactive potential of Chilean BB and supports the evidence that this bee product is a promising source of antioxidants and antimicrobial compounds.

Binuclear Biphenyl Organogold(III) Complexes: Synthesis, Photophysical and Theoretical Investigation, and Anticancer Activity

Posted on 13 September 2023 by

Four binuclear Au(III) complexes have been synthetized using non-chelating bidentate ligands. When a chelating ligand was used, a digold salt was obtained resulting from the chelation of the diphosphine ligand on one Au moiety and a [(C^C)AuCl₂]⁻ anion. The complexes appeared strongly emissive in solid state and the digold salt presented anticancer activities in the nanomolar range with no modification of the [(C^C)Au(P^P)]⁺ in the presence of biomolecules.

Abstract

A series of four binuclear complexes of general formula [(C^C)Au(Cl)(L^L)(Cl)Au(C^C)], where C^C is 4,4’-diterbutylbiphenyl and L^L is either a bridging diphosphine or 4,4’-bipyridine, are synthetized with 52 to 72 % yield and structurally characterized by X-ray diffraction. The use of the chelating 1,2-diphenylphosphinoethane ligand in a 1 : 2 (P^P):Au stoichiometry leads to the near quantitative formation of a gold double-complex salt of general formula [(C^C)Au(P^P)][(C^C^)AuCl₂]. The compounds display long-lived yellow-green phosphorescence with λ_em in the range of 525 to 585 nm in the solid state with photoluminescence quantum yields (PLQY) up to 10 %. These Au^III complexes are tested for their antiproliferative activity against lung adenocarcinoma cells A549 and results show that compounds 2 and 5 are the most promising candidates. The digold salt 5 shows anticancer activity between 66 and 200 nM on the tested cancer cell lines, whereas derivative 2 displays concentration values required to reduce by 50 % the cell viability (IC₅₀) between 7 and 11 μM. Reactivity studies of compound 5 reveal that the [(C^C)Au(P^P)]⁺ cation is stable in the presence of relevant biomolecules including glutathione suggesting a structural mechanism of action.

Mechanochemical difluoromethylation of (thio)phenols and N‐heterocycles

Posted on 13 September 2023 by nJoseph Ford, nBenjamin Hopkin, nJeroen B. I. Sap, nVéronique Gouverneurn

Abstract

Herein, we report a minimalistic protocol for the solvent-free, mechanochemical difluoromethylation of (thio)phenols and N-heteroarenes using non-ozone depleting chlorodifluoromethyl phenyl sulfone as a difluorocarbene source. This mechanochemical difluoromethylation features a short reaction time, excellent functional group tolerance, and compatibility with complex biologically active scaffolds.

Targeting AKT2 site in MDA‐MB‐231 cells by pyrazole hybrids: Structural, biological and molecular docking studies

Posted on 13 September 2023 by

: Pyrazolic hybrids appended with naphthalene, p-chlorobenzene, o-phenol and toluene have been synthesized using Claisen Schmidt condensation reaction of 1-benzyl-3,5-dimethyl-1H-pyrazole-4-carbaldehyde. All compounds were characterized by various spectroscopic techniques. Compound (E)-3-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-1-(4-chlorophenyl)prop-2-en-1-one crystallizes in monoclinic crystal system with C2/c space group. These synthesized compounds were tested for cytotoxic activity and among these compounds 4b and 5a shows prominent cytotoxic activity against triple-negative breast cancer (TNBC) cells MDA-MB-231 with IC50 values 47.72 µM and 24.25 µM respectively. Distinguishing morphological changes were noticed in MDA-MB-231 cells treated with pyrazole hybrids contributing to apoptosis action. To get more insight into cytotoxic activity, in silico molecular docking of these compounds were performed and the results suggested that (E)-3-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-1-(p-tolyl)prop-2-en-1-one and 1-(1'-benzyl-5-(4-chlorophenyl)-3',5'-dimethyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazol]-2-yl)ethan-1-one binds to the prominent domain of Akt2 indicating their potential ability as Akt2 inhibitor. Moreover, from in silico ADME studies clearly demonstrated that these compounds may be regarded as a drug candidate for sub-lingual absorption based on log p values (2.157- 4.924). These compounds also show promising antitubercular activity. The overall results suggest that pyrazolic hybrids with substitution at less sterically hindered positions have appealing potent cytotoxic activity and antituberculosis activity due to which they may act as multidrug candidate.

State‐selected photo‐recombination cross sections of H‐like ions in the KLL resonant energy range

Posted on 13 September 2023 by nK Ma, nY Chun

The total and partial cross sections of PR are calculated for the H-like ions with electron energies covering KLL resonant region. The results show that the shape of the partial PR cross sections strongly depends on the recombined final state, where the partial cross-section shape exhibits obvious asymmetry. Moreover, the eigenphase was provided for each PR channel as an important scattering parameter, which can be used to study the time delay of the scattering process.

Abstract

We theoretically study the state-selected photo-recombination process of highly charged ions using the close-coupling approximation and the full relativistic Dirac R-matrix method combined with the Dirac Atomic R-matrix Codes (DARC). Focusing on the interference between the direct and indirect processes and the relativistic effects on the spin-orbit splitting, we calculate the total and partial photo-recombination cross sections of the H-like Ne9+$$ {}^{9+} $$, Cl16+$$ {}^{16+} $$, Fe25+$$ {}^{25+} $$, and Kr35+$$ {}^{35+} $$ ions. The energies of the incident electrons are considered as in the KLL$$ KLL $$ resonant regions, in which the initial state is the 1s$$ 1s $$ ground state of the H-like ions and the recombined states includes the ground state (1s2)1S0$$ {\left(1{s}^2\right)}^1{S}_0 $$ and six lower excited states (1s2s)1S0,3S1$$ {(1s2s)}^1{S}_0{,}^3{S}_1 $$, and (1s2p)3P0,1,2,1P1$$ {(1s2p)}^3{P}_{0,1,2},{\kern0.3em }^1{P}_1 $$ of the He-like ions. We utilize the multi-configuration Dirac-Fock method to calculate the target state wavefunctions, transition energies, and transition probabilities of both the one-electron one-photon (OEOP) and two-electron one-photon (TEOP) transitions from the resonant captured states to the recombined states. By analyzing the calculated atomic data, we identify all resonant peaks in each partial photo-recombination process, and our results agree well with the available results in literature. Our study reveals a significant interference effect in the photo-recombination cross sections, especially in the partial cross sections. Moreover, we present the eigenphase as a function of the electron energy for each partial photo-recombination channel.

Photo‐induced Desulfurative Processes for Carbon Radical Generation

Posted on 13 September 2023 by

Photo-initiated desulfurization of sulfur-containing derivatives such as, native thiols, thioethers, sulfonium salts and xanthates, allows the generation of carbon-based radicals that can be coupled with various partners providing access to a wide range of functionalized molecules by C−C and C-heteroatom bond formation.

Abstract

Thiols constitute an important family among sulfur-containing compounds, with well-established applications in various fields ranging from medicine to material science. For instance, thiol residues are good hydrogen donors which reduce radical species in biological or chemical processes. However, even though the S−H bond activation of thiols for providing access to thiyl radicals has been largely studied, desulfurative processes affording carbon-based radicals by C−S bond activation have been less explored. In recent years, photoredox catalysis has become the prevalent method for the generation of radicals under soft reaction conditions from readily available starting materials under visible light. In this context, recent studies have been devoted to the development of photocatalytic procedures aiming at the desulfurization of thiol derivatives leading to new C−H, C−C or C-Het bond formation reactions. This review will cover the synthetic methodologies and strategies for photo-mediated desulfurization of native thiols, thioethers, sulfonium salts and xanthates to access new organic compounds. This emerging field is especially interesting for new transformations of cysteine and peptide derivatives.

Computation‐Based Design of Salt Bridges in PETase for Enhanced Thermostability and Performance for PET Degradation

Posted on 13 September 2023 by nZhi Qu, nKun Chen, nLin Zhang, nYan Sunn

Amino acid residues with opposite charges were introduced into the flexible region of IsPETase using a computation-based salt bridge design strategy. The mutation sites formed a salt bridge or salt bridge network to improve the thermal stability of IsPETase, and the degradation efficiency of amorphous PET film was enhanced.

Abstract

Polyethylene terephthalate (PET) is one of the most widely used plastics, and the accumulation of PET poses a great threat to the environment. IsPETase can degrade PET rapidly at moderate temperatures, but its application is greatly limited by the low stability. Herein, molecular dynamics (MD) simulations combined with a sequence alignment strategy were adopted to introduce salt bridges into the flexible region of IsPETase to improve its thermal stability. In the designed variants, the T _m values of IsPETase^I168R/S188D and IsPETase^I168R/S188E were 7.4 and 8.7 °C higher than that of the wild type, respectively. The release of products degraded by IsPETase^I168R/S188E was 4.3 times that of the wild type. Tertiary structure characterization demonstrated that the structure of the variants IsPETase^I168R/S188D and IsPETase^I168R/S188E became more compact. Extensive MD simulations verified that a stable salt bridge was formed between the residue R168 and D186 in IsPETase^I168R/S188D, while in IsPETase^I168R/S188E an R168-D186-E188 salt bridge network was observed. These results confirmed that the proposed computation-based salt bridge design strategy could efficiently generate variants with enhanced thermal stability for the long-term degradation of PET, which would be helpful for the design of enzymes with improved stability.

Terpene Synthases in the Biosynthesis of Drimane‐Type Sesquiterpenes across Diverse Organisms

Posted on 13 September 2023 by nTzu‐Ho Chen, nHsiao‐Ching Linn

Drimane-type sesquiterpenes (DTSs) are bioactive natural products found in various organisms. We review the discovery of DTS synthases and the tailoring enzymes generating the chemical diversity. The catalytic motifs, domain functions and underlying mechanisms of the DTS synthases in constructing drimane scaffold are summarized. These discoveries present valuable opportunities for exploring DTSs biosynthesis through genome mining.

Abstract

Drimane-type sesquiterpenes (DTSs) are significant terpenoid natural products characterized by their unique C₁₅ bicyclic skeleton. They are produced by various organisms including plants, fungi, bacteria and marine organisms, and exhibit a diverse array of bioactivities. These bioactivities encompass antifeedant, anti-insecticidal, anti-bacterial, anti-fungal, anti-viral and anti-proliferative properties. Some DTSs contribute to the pungent flavor found in herb plants like water pepper, while others serve as active components responsible for the anti-cancer activities observed in medicinal mushrooms such as (−)-antrocin from Antrodia cinnamomea. Recently, DTS synthases have been identified in various organisms, biosynthesizing drimenol, drim-8-ene-11-ol and (+)-albicanol, which all possess the characteristic drimane skeleton. Interestingly, despite these enzymes producing chemical molecules with a drimane scaffold, they exhibit minimal amino acid sequence identity across different organisms. This Concept article focuses on the discovery of DTS synthases and the tailoring enzymes generating the chemical diversity of drimane natural products. We summarize and discuss their key features, including the chemical mechanisms, catalytic motifs and functional domains employed by these terpene synthases to generate DTS scaffolds.

A Cell‐Free Multi‐enzyme Cascade Reaction for the Synthesis of CDP‐Glycerol

Posted on 13 September 2023 by

A multi-enzyme cascade for the cell-free, one-pot synthesis of CDP-glycerol has been developed. Through a design-of-experiments approach, the yield of the cascade was increased from 10 to 89 % with respect to cytidine as a substrate. The final product titer after a batch time of 24 h was 31.2 mM CDP-glycerol.

Abstract

CDP-glycerol is a nucleotide-diphosphate-activated version of glycerol. In nature, it is required for the biosynthesis of teichoic acid in Gram-positive bacteria, which is an appealing target epitope for the development of new vaccines. Here, a cell-free multi-enzyme cascade was developed to synthetize nucleotide-activated glycerol from the inexpensive and readily available substrates cytidine and glycerol. The cascade comprises five recombinant enzymes expressed in Escherichia coli that were purified by immobilized metal affinity chromatography. As part of the cascade, ATP is regenerated in situ from polyphosphate to reduce synthesis costs. The enzymatic cascade was characterized at the laboratory scale, and the products were analyzed by high-performance anion-exchange chromatography (HPAEC)-UV and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). After the successful synthesis had been confirmed, a design-of-experiments approach was used to screen for optimal operation conditions (temperature, pH value and MgCl₂ concentration). Overall, a substrate conversion of 89 % was achieved with respect to the substrate cytidine.