Acyl Research Articles

Visible-Light-Induced Acylative Pyridylation of Styrenes.

A visible-light-induced photocatalyst-free acylative pyridylation of styrenes with 4-acyl-1,4-dihydropyridines (DHPs) and 4-cyanopyridines has been described, featuring mild reaction conditions, a broad substrate scope, and good functional group tolerance. The reaction could also be performed under sunlight irradiation albeit with a slightly lower conversion. 4-Acyl-1,4-DHPs serve a dual role, acting as both a photoreductant to reduce the cyanopyridine to its radical anion intermediate and a radical precursor to produce the acyl radical. The mechanism was especially elucidated through the Hammett analysis, with the quadratic linear regression analysis by using radical dual parameters, σmb and σjj·. The findings from Hammett analysis further demonstrate that the rate-limiting step of the process is the single electron transfer between 4-acyl-1,4-DHPs and 4-cyanopyridines.

Dynamics of acyl carrier protein in de novo fatty acid synthesis by Enterococcus faecalis based on NMR spectroscopy and molecular dynamics simulation

Fatty acid synthesis (FAS) is essential for the production of biological components such as cell membrane building blocks and metabolism-related compounds. There are two types of bacterial FAS: de novo FAS and FAS through the incorporation of external fatty acids. Enterococcus faecalis possesses two distinct acyl carrier proteins (ACPs), AcpA (EfAcpA) and AcpB (EfAcpB), which serve as cofactors in the two types of FAS. We previously showed through NMR spectroscopy that EfAcpA comprises only three long helices, while EfAcpB consists of four helices, including a short α3 helix, similar to other bacterial ACPs. An increase in melting temperature (Tm) from 64.0 to 76.1 °C confirmed that protein structural stability increased in the presence of calcium ions. Using NMR spectroscopy, two metal binding sites were identified in EfAcpA: site A was located at the start of the α2 helix while site B was situated near the α2 helix and α2α3 loop. To understand the importance of structural flexibility of EfAcpA in de novo FAS, we investigated its motional properties using backbone spin relaxation and molecular dynamics simulations. The α2α3 loop in EfAcpA displayed high flexibility, as indicated by low heteronuclear NOE values. The residues Val51, Glu54, and Gly58 exhibited significant R2 values, likely due to the movement of this loop. EfAcpA created a novel cavity towards the α1α2 loop, in contrast to conventional cavity formation in most bacterial ACPs. This unique behavior was attributed to the flexibility exhibited by the α2α3 loop. The structural and motional characteristics of EfAcpA confirmed that its conformational plasticity is a crucial factor influencing acyl chain transfers in de novo FAS. Given the increasing antibiotic resistance observed for E. faecalis in clinical settings, the findings of this study may contribute to the development of more effective pathogen management strategies targeting FAS.

Synthesis of thioesters using an electrochemical three-component reaction involving elemental sulfur.

An electrochemical three-component reaction involving elemental sulfur is disclosed for achieving a metal-free, oxidant-free synthesis of thioesters in a high atom-economical, step-economical and chemoselective manner. A mechanistic investigation indicates that the use of elemental sulfur to trap acyl radical derived from radical umpolung of α-keto acid with an electrochemical design can efficiently generate a carbonyl thiyl radical, which can further be captured by diazoalkane to afford various thioesters.

Controlling the formation of ionic complex vesicles through double-tailed surfactants.

Liposomes are often used in cosmetics since they are naturally derived and have excellent texture enhancing capabilities. However, when preparing them by using phospholipids with unsaturated acyl groups, they easily suffer from oxidative degradation. Accordingly, hydrogenated phospholipids are preferred, however, it is difficult to prepare stable liposomes due to its high gel-liquid crystalline phase transition temperature. On the other hand, although dialkyl dimethyl ammonium type cationic surfactants are widely known to form vesicles, they have rarely been used for skincare products except for water-in-oil type emulsion creams stabilized by organically modified clay minerals. We decided to overcome all of the problems above through ionic complex vesicles formed by double-tailed cationic and anionic surfactants. Distearyl dimethyl ammonium chloride (DSAC) and sodium dilauramidoglutamide lysine (DLGL) were selected as cationic and anionic surfactants, respectively. Differential scanning calorimetry (DSC) and small- and wide-angle X-ray scattering (SWAXS) measurements were performed to confirm the DSAC/DLGL/water ternary phase diagram. Newly developed ionic complex vesicle formation was confirmed by cryogenic transmission electron microscopy (cryo-TEM). The adsorbed cosmetic film structure on the skin invivo was evaluated through the polarized infrared external reflection (PIR-ER). Finally, a cosmetic lotion formula was developed and the vesicle size was determined by dynamic light scattering (DLS). DSC and SWAXS data indicated that stable vesicles could be obtained at a molar ratio of DLGL to DSAC = 6:4. At this molar ratio, multi lamellar vesicles with diameters less than 100 nm were observed through cryo-TEM. PIR-ER data revealed that the developed vesicles formed a highly perpendicular orientation to the human skin surface. We have succeeded in formulating a cosmetic lotion containing developed vesicles with a mean diameter of 63.2 nm, which was stable over 1 month at 0, 37, and 50°C. Our newly developed vesicles can be easily obtained through a coagulation process. Also, the adsorbed film structure supported by PIR-ER experiments implies that the developed lotion has an excellent texture that is the same as cosmetic lotions containing liposomes. Therefore, it's possible that this ionic complex vesicle could take the place of liposomes.

Nickel‐Catalyzed Highly Selective Radical C‐C Coupling from Carboxylic Acids with Photoredox Catalysis

The selective coupling of two different radicals is a long‐standing challenge due to the process occurring statistically. Generally, the cross‐coupling selectivity is achieved by the persistent radical effect (PRE), resulting in limited radical precursors. In this paper, a highly selective cross‐coupling of alkyl radicals with acyl radicals to construct C(sp2)‐C(sp3) bonds, or with alkyl radicals to construct C(sp3)‐C(sp3) bonds have been achieved with the readily available carboxylic acids and their derivatives (NHPI ester) as coupling partners. The success originates from the use of tridentate ligand (L1) to enable radical cross‐coupling process to Ni‐mediated organometallic mechanism. This protocol offers a facile and flexible access to structurally diverse ketones (up to 90% yield), and also a new solution for the challenging double decarboxylative C(sp3)‐C(sp3) coupling. The broad utility and functional group tolerance are further illustrated by the late‐stage functionalization of natural‐occurring carboxylic acids and drugs.

Nickel-Catalyzed Highly Selective Radical C-C Coupling from Carboxylic Acids with Photoredox Catalysis.

The selective coupling of two different radicals is a long-standing challenge due to the process occurring statistically. Generally, the cross-coupling selectivity is achieved by the persistent radical effect (PRE), resulting in limited radical precursors. In this paper, a highly selective cross-coupling of alkyl radicals with acyl radicals to construct C(sp2)-C(sp3) bonds, or with alkyl radicals to construct C(sp3)-C(sp3) bonds have been achieved with the readily available carboxylic acids and their derivatives (NHPI ester) as coupling partners. The success originates from the use of tridentate ligand (L1) to enable radical cross-coupling process to Ni-mediated organometallic mechanism. This protocol offers a facile and flexible access to structurally diverse ketones (up to 90% yield), and also a new solution for the challenging double decarboxylative C(sp3)-C(sp3) coupling. The broad utility and functional group tolerance are further illustrated by the late-stage functionalization of natural-occurring carboxylic acids and drugs.

Plasticity of the Arabidopsis leaf lipidome and proteome in response to pathogen infection and heat stress.

Plants must cope with a variety of stressors during their life cycle, and the adaptive responses to these environmental cues involve all cellular organelles. Among them, comparatively little is known about the contribution of cytosolic lipid droplets (LDs) and their core set of neutral lipids and associated surface proteins to the rewiring of cellular processes in response to stress. Here, we analyzed the changes that occur in the lipidome and proteome of Arabidopsis (Arabidopsis thaliana) leaves after pathogen infection with Botrytis cinerea or Pseudomonas syringae, or after heat stress. Analyses were carried out in wild-type plants and the oil-rich double mutant trigalactosyldiacylglycerol1-1 sugar dependent 1-4 (tgd1-1 sdp1-4) that allowed for an allied study of the LD proteome in stressed leaves. Using liquid chromatography-tandem mass spectrometry-based methods, we showed that a hyperaccumulation of the primary LD core lipid triacylglycerol is a general response to stress and that acyl chain and sterol composition are remodeled during cellular adaptation. Likewise, comparative analysis of the LD protein composition in stress-treated leaves highlighted the plasticity of the LD proteome as part of the general stress response. We further identified at least two additional LD-associated proteins, whose localization to LDs in leaves was confirmed by confocal microscopy of fluorescent protein fusions. Taken together, these results highlight LDs as dynamic contributors to the cellular adaptation processes that underlie how plants respond to environmental stress.

Increased phosphatidylcholine and its hydroperoxides in serum low-density lipoproteins from patients with non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease is classified into simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) according to histological findings from liver biopsies. Phosphatidylcholine (PC), the main component of phospholipids in serum lipoproteins, is easily oxidized to phosphatidylcholine hydroperoxide (PC-OOH). Although a lipid composition in the low-density lipoproteins (LDL) from patients with NASH could be abnormal, it remains unclear. Here, to better understand the characteristics of lipids in the LDL from NASH and SS, we compared the composition of PC and PC-OOH species in LDL particles (LDL-PC, LDL-PCOOH) from these patients, then clarified the association between these lipids and NASH severity. The serum samples from patients with NASH (female, n = 9) and SS (female, n = 4; male, n = 2) were used for isolation of LDL. Total lipids were extracted from isolated LDL, and the species of PC and PC-OOH were measured using liquid chromatography-mass spectrometry/mass spectrometry. The sum of LDL-PC and the sum of LDL-PCOOH were significantly higher in NASH than in SS. Several LDL-PC (PC 32:0, 32:1, 32:2, 34:3, 36:2, sum of PC with saturated fatty acyl chains and sum of LDL-PC with polyunsaturated fatty acyl chains) and several LDL-PCOOH (34:2, 36:2, 36:3 and total) were increased significantly with increasing fibrosis score. In particular, a series of LDL-PCOOH were more reflective of the severity of fibrosis score. LDL-PC and LDL-PCOOH species were strongly correlated with the fibrosis score in NASH, which suggests that abnormal LDL is involved in the development of liver fibrosis.

Phosphatidylcholine levels regulate hyphal elongation and differentiation in the filamentous fungus Aspergillus oryzae

Filamentous fungi are eukaryotic microorganisms that differentiate into diverse cellular forms. Recent research demonstrated that phospholipid homeostasis is crucial for the morphogenesis of filamentous fungi. However, phospholipids involved in the morphological regulation are yet to be systematically analyzed. In this study, we artificially controlled the amount of phosphatidylcholine (PC), a primary membrane lipid in many eukaryotes, in a filamentous fungus Aspergillus oryzae, by deleting the genes involved in PC synthesis or by repressing their expression. Under the condition where only a small amount of PC was synthesized, A. oryzae hardly formed aerial hyphae, the basic structures for asexual development. In contrast, hyphae were formed on the surface or in the interior of agar media (we collectively called substrate hyphae) under the same conditions. Furthermore, we demonstrated that supplying sufficient choline to the media led to the formation of aerial hyphae from the substrate hyphae. We suggested that acyl chains in PC were shorter in the substrate hyphae than in the aerial hyphae by utilizing the strain in which intracellular PC levels were controlled. Our findings suggested that the PC levels regulate hyphal elongation and differentiation processes in A. oryzae and that phospholipid composition varied depending on the hyphal types.

Cryptotanshinone-Induced Permeabilization of Model Phospholipid Membranes: A Biophysical Study

The Danshen terpenoid cryptotanshinone (CPT) is gaining enormous interest in light of its various outstanding biological activities. Among those, CPT has been shown to interact with cell membranes and, for instance, to have antibacterial activity. Several works have shown that CPT alone, or in combination with other drugs, can effectively act as an antibiotic against various infectious bacteria. Some authors have related the mechanism underlying this action to CPT–membrane interaction. This work shows that CPT readily partitions into phosphatidylcholine membranes, but there is a limiting capacity of accommodation of ca. 1 mol CPT to 3 mol phospholipid. The addition of CPT to unilamellar liposomes composed of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) causes membrane permeabilization, as shown by fluorescent probe leakage. This process has been kinetically studied, as well as its modulation by incorporation of phosphatidylethanolamine or phosphatidylglycerol, as a model for pathogenic cell membranes. The thermotropic behavior of 1,2-dimyristoylphosphatidylcholine (DMPC) model membranes is weakly affected by CPT, but the terpenoid causes significant dehydration of the polar region of the bilayer and weak disordering of the acyl chain palisade, as observed in Fourier-transform infrared spectroscopy (FTIR) results. Small-angle X-ray scattering (SAXS) shows that CPT increases DMPC bilayer thickness, which could be due to localization near the phospholipid/water interface. Molecular dynamics (MD) simulations show that the lateral diffusion coefficient of the phospholipid increases with the presence of CPT. CPT extends from the polar head region to the center of the bilayer, being centered between the carbonyl groups and the unsaturated region of the POPC, where there is greater overlap. Interestingly, the free energy profiles of a water molecule crossing the lipid membrane show that the POPC membrane becomes more permeable in the presence of CPT. In summary, our results show that CPT perturbs the physicochemical properties of the phospholipid membrane and compromises its barrier function, which could be of relevance to explain part of its antimicrobial or anticancer activities.

Organocatalyzed Photoelectrochemistry for the Generation of Acyl and Phosphoryl Radicals through Hydrogen Atom-Transfer Process.

An organocatalyzed photoelectrochemical method for the generation of acyl and phosphoryl radicals from formamides, aldehydes, and phosphine oxides has been developed. This protocol utilizes 9,10-phenanthrenequinone (PQ) as both a molecular catalyst and a hydrogen atom-transfer (HAT) reagent, eliminating the requirement for external metal-based reagents, HAT reagents, and oxidants. The generated acyl radicals can be applied to a range of radical-mediated transformation reactions, including C-H carbamoylation of heteroarenes, intermolecular tandem radical cyclization of CF3-substituted N-arylacrylamides, as well as intramolecular cyclization reactions. The use of acyl radicals in these transformations offers an efficient and sustainable approach to accessing structurally diverse carbonyl compounds.

An Effective Method for the Evaluation of the Enantiomeric Purity of 1,2-Diacyl-sn-glycero-3-phosphocholine-Based Lipids by NMR Analysis

In this article, we report a very efficient method for the determination of the enantiopurity of 1,2-diacyl-sn-glycero-3-phosphocholine by 1H NMR analysis using a readily available chiral derivatizing boronic acid (CDA), (R)-(2-(((1-phenylethyl)amino)methyl)phenyl)boronic acid. After the removal of the acyl groups of 1,2-diacyl-sn-glycero-3-phosphocholine via methanolysis and washing fatty acid byproducts with CHCl3, the obtained sn-glycero-3-phosphocholine (GPC) with the free diol moiety is derivatized by the chiral boronic acid and analyzed by 1H NMR analysis. The choline methyl resonance of each diastereomer is observed at distinctive chemical shifts in the 1H NMR spectrum. Integration of the respective resonances allows direct determination of the enantiomeric purity. The procedure was tested successfully using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) with different enantiomeric purities and with commercially available 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).

YdbH and YnbE form an intermembrane bridge to maintain lipid homeostasis in the outer membrane of Escherichia coli

The outer membrane (OM) of didermic gram-negative bacteria is essential for growth, maintenance of cellular integrity, and innate resistance to many antimicrobials. Its asymmetric lipid distribution, with phospholipids in the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet, is required for these functions. Lpt proteins form a transenvelope bridge that transports newly synthesized LPS from the inner membrane (IM) to OM, but how the bulk of phospholipids are transported between these membranes is poorly understood. Recently, three members of the AsmA-like protein family, TamB, YhdP, and YdbH, were shown to be functionally redundant and were proposed to transport phospholipids between IM and OM in Escherichia coli. These proteins belong to the repeating β-groove superfamily, which includes eukaryotic lipid-transfer proteins that mediate phospholipid transport between organelles at contact sites. Here, we show that the IM-anchored YdbH protein interacts with the OM lipoprotein YnbE to form a functional protein bridge between the IM and OM in E. coli. Based on AlphaFold-Multimer predictions, genetic data, and in vivo site-directed cross-linking, we propose that YnbE interacts with YdbH through β-strand augmentation to extend the continuous hydrophobic β-groove of YdbH that is thought to shield acyl chains of phospholipids as they travel through the aqueous intermembrane periplasmic compartment. Our data also suggest that the periplasmic protein YdbL prevents extensive amyloid-like multimerization of YnbE in cells. We, therefore, propose that YdbL has a chaperone-like function that prevents uncontrolled runaway multimerization of YnbE to ensure the proper formation of the YdbH-YnbE intermembrane bridge.

Decarbonylative and Dehydrogenative Cascade Annulation of N‐(o‐cyanobiaryl)acrylamides with Aldehydes

Decarbonylative and dehydrogenative cascade annulation of aldehydes with N‐(o‐cyanobiaryl)acrylamides have been developed for the synthesis of a broad spectrum of alkyl‐ and carbonyl‐substituted pyrido[4,3,2‐gh]phenanthridines. Secondary and tertiary aldehydes can undergo decarbonylative cascade under DTBP/malonic acid conditions, while aryl, primary and secondary aldehydes can undergo dehydrogenative reaction under TBHP system. Such transformations were triggered by alkyl and acyl radicals, and the annulations were accomplished through intramolecular additions of carbon‐centered radical to nitrile group and iminyl radical to aromatic ring.

Different lateral packing stress in acyl chains alters KcsA orientation and structure in lipid membranes

The molecular structures of the various intrinsic lipids in membranes regulate lipid-protein interactions. These different lipid structures with unique volumes produce different lipid molecular packing stresses/lateral stresses in lipid membranes. Most studies examining lipid packing effects have used phosphatidylcholine and phosphatidylethanolamine (PE), which are the main phospholipids of eukaryotic cell membranes. In contrast, Gram-negative or Gram-positive bacterial membranes are composed primarily of phosphatidylglycerol (PG) and PE, and the physical and thermodynamic properties of each acyl chain in PG at the molecular level remain unresolved. In this study, we used 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (POPG, 16:0–18:1 PG) and 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (PAPG, 16:0–20:4 PG) to prepare lipid bilayers (liposome) with the rod-type fluorescence probe DPH. We measured the lipid packing conditions by determining the rotational freedom of DPH in POPG or PAPG bilayers. Furthermore, we investigated the effect of different monoacyl chains on a K+ channel (KcsA) structure when embedded in POPG or PAPG membranes. The results revealed that differences in the number of double bonds and carbon chain length in the monoacyl chain at sn-2 affected the physicochemical properties of the membrane and the structure and orientation of KcsA.

Effect of cardiolipin on the lamellarity and elongation of liposomes hydrated in PBS

Lamellarity and shape are important factors in the formation of vesicles and determine their role in biological systems and pharmaceutical applications. Cardiolipin (CL) is a major lipid in many biological membranes and exerts a great influence on their structural organization due to its particular structure and physico-chemical properties. Here, we used small-angle X-ray and neutron scattering to study the effects of CL with different acyl chain lengths and saturations (CL14:0, CL18:1, CL18:2) on vesicle morphology and lamellarity in membrane models containing mixtures of phosphatidylcholine and phosphatidylethanolamine with different acyl chain lengths and saturations (C14:0 and C 18:1). Measurements were performed in the presence of Phosphate Buffer Saline (PBS), at 37°C, to better reflect physiological conditions, which resulted in strong effects on vesicle morphology, depending on the type and amount of CL used. The presence of small quantities of CL (from 2.5%) reduced inter-membrane correlations and increased perturbation of the membrane, an effect which is enhanced in the presence of matched shorter saturated acyl chains, and mainly unilamellar vesicles (ULV) are formed. In extruded vesicles, employed for SANS experiments, flattened vesicles are observed partly due to the hypertonic effect of PBS, but also influenced by the type of CL added.Our experimental data from SAXS and SANS revealed a strong dependence on CL content in shaping the membrane microstructure, with an apparent optimum in the PC:CL mixture in terms of promoting reduced correlations, preferred curvature and elongation. However, the use of PBS caused distinct differences from previously published studies in water in terms of vesicle shape, and highlights the need to investigate vesicle formation under physiological conditions in order to be able to draw conclusions about membrane formation in biological systems.

Lipidomics and single-cell RNA sequencing reveal lipid and cell dynamics of porcine glycerol-injured skeletal muscle regeneration model

AimsIntramuscular fat (IMF) infiltration and extracellular matrix (ECM) deposition are characteristic features of muscle dysfunction, such as muscular dystrophy and severe muscle injuries. However, the underlying mechanisms of cellular origin, adipocyte formation and fibrosis in skeletal muscle are still unclear. Main methodsPigs were injected with 50 % glycerol (GLY) to induce skeletal muscle injury and regeneration. The acyl chain composition was analyzed by lipidomics, and the cell atlas and molecular signatures were revealed via single-cell RNA sequencing (scRNA-seq). Adipogenesis analysis was performed on fibroblast/fibro-adipogenic progenitors (FAPs) isolated from pigs. Key findingsThe porcine GLY-injured skeletal muscle regeneration model was characterized by IMF infiltration and ECM deposition. Skeletal muscle stem cells (MuSCs) and FAP clusters were analyzed to explore the potential mechanisms of adipogenesis and fibrosis, and it was found that the TGF-β signaling pathway might be a key switch that regulates differentiation. Consistently, activation of the TGF-β signaling pathway increased SMAD2/3 phosphorylation and inhibited adipogenesis in FAPs, while inhibition of the TGF-β signaling pathway increased the expression of PPARγ and promoted adipogenesis. SignificanceGLY-induced muscle injury and regeneration provides comprehensive insights for the development of therapies for human skeletal muscle dysfunction and fatty infiltration-related diseases in which the TGF-β/SMAD signaling pathway might play a primary regulatory role.

Lipidomics reveals the reshaping of the mitochondrial phospholipid profile in cells lacking OPA1 and Mitofusins

Depletion or mutations of key proteins for mitochondrial fusion, like optic atrophy 1 (OPA1) and Mitofusins 1 and 2 (Mfn 1 and 2), are known to significantly impact the mitochondrial ultrastructure, suggesting alterations of their membranes’ lipid profiles. In order to make an insight into this issue, we used hydrophilic interaction liquid chromatography (HILIC) coupled with electrospray ionization-high resolution mass spectrometry to investigate the mitochondrial phospholipid (PL) profile of mouse embryonic fibroblasts (MEFs) knocked out for OPA1 and Mfn1/2 genes. 167 different sum compositions were recognized for the four major PL classes of mitochondria, namely phosphatidylcholines (PC, 63), phosphatidylethanolamines (PE, 55), phosphatidylinositols (PI, 21) and cardiolipins (CL, 28). A slight decrease in the CL/PC ratio was found for Mfn1/2-knock out mitochondria. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were subsequently used to further process HILIC-ESI-MS data. A progressive decrease in the incidence of alk(en)yl/acyl species in PC and PE classes and a general increase in the incidence of unsaturated acyl chains across all the investigated PL classes was inferred in OPA1 and Mfn1/2 knockouts compared to wild-type MEFs. These findings suggest a reshaping of the PL profile consistent with the changes observed in the mitochondrial ultrastructure when fusion proteins are absent. Based on the existing knowledge on the metabolism of mitochondrial phospholipids, we propose that fusion proteins, especially mitofusins, might influence the PL transfer between the mitochondria and the endoplasmic reticulum, likely in the context of mitochondria-associated membranes (MAMs).

Controlled dual release of phenol compounds from phospholipid complexes of short-chain lipophenols

Ethanol evaporation method was applied to synthesize phospholipid complexes from phosphatidylcholine (PC) and short-chain alkyl gallates (A-GAs, a typical representative of lipophenols) including butyl-, propyl- and ethyl gallates. 1H NMR, UV and FTIR showed that A-GAs were interacted with PC through weak physical interaction. Through the analysis of concentrations of A-GAs and gallic acid (GA) by an everted rat gut sac model coupled with HPLC-UV detection, phospholipid complexes were found to gradually release A-GAs. These liberated A-GAs were further hydrolyzed by intestinal lipases to release GA. Both of GA and A-GAs could cross intestinal membrane. Especially, the transmembrane A-GAs could also be hydrolyzed to produce GA. Undoubtedly, the dual release of phenol compounds from phospholipid complexes of short-chain lipophenols will be effective to extend the in vivo residence period of phenol compounds. More importantly, such behavior is easily adjusted by changing the acyl chain lengths of lipophenols in phospholipid complexes.

5-O-Acetylpinostrobin derivatives inhibit estrogen alpha and progesterone receptors through a molecular docking approach

Background: Among all cancers, breast cancer accounts for 11.7% of new cases and 6.9% of deaths worldwide. This is driven by increased estrogen receptor alpha (ERα) and progesterone receptor (PgR) expression. Many breast cancer drugs cause various side effects. Modifying the structure of pinostrobin by adding acyl groups to obtain 5-O-acetylpinostrobin derivatives can increase its activity and selectivity. Objective: This study aimed to predict the interaction of 5-O-acetylpinostrobin derivatives with ERα and PgR. Method: A molecular docking approach using AutodockTool. The Protein Data Bank (PDB) was used to obtain ID 3ERT (ERα) and 2W8Y (PgR). Result: The analysis showed the value of free energy binding (ΔG) to ERα with a range of -8.58 to -5.76 kcal/mol and an inhibition concentration (Ki) of 0.51 to 59.91 μM. PgR had ΔG values of -12.37 to -8.30 kcal/mol and Ki of 0.86 to 830.64 nM. Conclusion: The study showed that 5-O-4-(dimethylamino)benzoylpinostrobin, 5-O-cyclohexancarbonylpinostrobin, 5-O-2-phenylacetylpinostrobin, 5-O-3-phenylpropanoylpinostrobin, and 5-O-cyclobutanecarbonylpinostrobin have the potential to be synthesised and serve as the basis for the development of new anticancer compounds that inhibit ERα and PgR in breast cancer.