Search Results (84)

The objective of this study is to evaluate, for the first time, the chemical composition and the antioxidant, enzyme inhibitory, photoprotective and antibacterial properties of the Tamarix boveana essential oil (EO) as well as its organic extracts. The analysis of the EO obtained from the aerial parts of T. boveana was carried out employing the technique of gas chromatography with flame ionization detection (GC-FID) and mass spectrometry (GC-MS). Forty-four constituents were identified, constituting 91.18% of the oil, with the major compounds being γ-cadinene (9.41%), β-caryophyllene (6.71%), limonene (6.5%), p-cymene (6.16%), copaene (4.37%), terpinen-4-ol (4.23%), δ-cadinene (4.21%) and γ-terpinene (4.11%). The antioxidant activity of T. boveana essential oil and organic extracts (hydroalcoholic, CHCl₃, AcOEt, n-BuOH) was evaluated by different tests, including DPPH, ABTS, phenanthroline, SNP and ferric reducing power. The findings indicated that T. boveana essential oil possesses moderate antioxidant capacity, with IC₅₀ values of 223.59 ± 1.01 μg/mL according to the DPPH test. The extracts and essential oil also demonstrated notable inhibitory impacts against α-amylase and butyrylcholinesterase. Antimicrobial activity was determined regarding four bacterial strains, determining the minimum inhibitory concentrations (MICs) and bactericidal concentrations (MBCs). The geometry and electronic properties of the main EO compounds were determined using density functional theory (DFT) calculations. Furthermore, docking studies were conducted to investigate the interaction and binding affinity of these molecules with the active sites of BuChE and α-amylase enzymes. The results highlight the value of Tamarix boveana as a medicinal plant and indicate its effectiveness as an important source of bioactive compounds for many uses. Full article

An aqueous mixture of three compounds (atrazine, carbamazepine, and p-chlorobenzoic acid) has been treated by photochemical processes including photolysis and photocatalysis with 10.7% TiO₂ supported on ceramic foams of mullite. Experiments were conducted in both ultrapure water and in a secondary effluent from a municipal wastewater treatment plant. Radiation at 365 nm was totally inefficient in the photolytic process carried out in ultrapure water; however, some sensitization phenomena were observed when municipal wastewater was used as a bulk matrix. In the latter case, conversion values in the range of 20–30% were obtained after 2 h. The photocatalytic process was much more effective experiencing conversions above 80% after just 80 min of reaction. The nature of the matrix used exerted a significant influence. Use of municipal wastewater slowed down the process due to the scavenging character of the natural organic matter content. Test runs in the presence of carbonates and t-butyl alcohol suggested that radical carbonates play some role in contaminant abatement, and secondary radicals generated after the t-BuOH attack by HO^● radicals should also be considered in the reaction mechanism. A pseudo-empirical mechanism of reactions sustains the experimental result obtained, acceptably modeling the effects of a water matrix, scavenger addition, and radiation volumetric photon flux. Full article

Three new amide-preformed triphenylamine-diamine monomers, namely 4,4′-bis(p-aminobenzamido)triphenylamine (4), 4,4′-bis(p-aminobenzamido)-4″-methoxytriphenylamine (MeO-4), and 4,4′-bis(p-aminobenzamido)-4″-tert-butyltriphenylamine (t-Bu-4), were synthesized and subsequently used to produce three series of electroactive aromatic poly(amide-imide)s (PAIs) via two-step polycondensation reactions with commercially available tetracarboxylic dianhydrides. Strong and flexible PAI films could be obtained by solution casting of the poly(amic acid) films followed by thermal imidization or direct solution casting from the organosoluble PAI samples. The PAIs had high glass-transition temperatures of 296–355 °C and showed no significant decomposition below 500 °C. The PAIs based on diamines MeO-4 and t-Bu-4 showed high electrochemical redox stability and strong color changes upon oxidation. For the PAIs derived from diamine 4, the TPA radical cation formed in situ during the electro-oxidative process could dimerize to a tetraphenylbenzidine structure, resulting in an additional oxidation state and color change. These PAIs exhibited increased solubility, lowered oxidation potentials, and enhanced redox stability compared to their polyimide analogs. Full article

Using the DFT method, an analogue of R,R-t-Bu-BenzP* was tried as a potential ligand for Ni-catalyzed asymmetric hydrogenation. This ligand contains benzyl groups instead of the t-Bu groups in R,R-t-Bu-BenzP*. Computational results imply that the R,R-Benz-BenzP* ligand (1) is expected to provide excellent enantioselectivity in the Ni-catalyzed asymmetric hydrogenation of 1-phenylethanone oxime. The computed effectiveness of the R,R-Benz-BenzP* ligand is stipulated by its conformational flexibility, which helps stabilize the crucial transition states via a non-bonding interaction between the substrate and the catalyst. R,R-Benz-BenzP* ligands with CN- and OMe-substituted benzyl rings were also computed to possess the same effectiveness. Full article

Background/Objectives: BuZhong Yiqi Formula (BZYQF) has significant ameliorative effects on type 2 diabetes mellitus (T2DM). However, its efficacy in alleviating the hyposalivation caused by T2DM needs to be confirmed, and its mechanism is unclear. Methods: Network pharmacology and molecular docking were combined to analyze the molecular mechanism by which BZYQF alleviates T2DM-caused hyposalivation. A T2DM rat model was induced to evaluate the efficacy of BZYQF. The total saliva before and after acid stimulation was collected to determine the salivary flow rate and salivary alpha-amylase (sAA) activity. The parotid (PG) and submandibular glands (SMG) of experimental rats were removed to perform histopathology observation, biochemical indicator determination, and expression detection of signaling molecules in the salivary secretion pathway. Results: The present study screened out 1014 potential targets of BZYQF regarding the treatment of T2DM. These targets were mainly involved in the formation of the receptor complex, exercising the neurotransmitter receptor activity and regulating secretion. They were significantly enriched in the salivary secretion pathway of β1-AR/PKA/AMY1 and CHRM3/IP3R/AQP5. Furthermore, in BZYQF, nine validated compounds were able to dock into the active site of β1-AR, and three validated compounds were able to dock into the active site of CHRM3. Animal experiments confirmed that BZYQF significantly reduces fasting blood glucose, total cholesterol and triglyceride levels; enhances insulin level and HOMA-IS (p < 0.05); and increases salivary flow rate (Basal: increase from 21.04 ± 14.31 to 42.65 ± 8.84 μL/min, effect size of Cohen’s d = 6.80, p = 0.0078; Stimulated: increase from 36.88 ± 17.48 to 72.63 ± 17.67 μL/min, effect size of Cohen’s d = 7.61, p = 0.0025) and sAA activity (Basal: increase from 0.68 ± 0.32 to 2.17 ± 0.77 U/mL, effect size of Cohen’s d = 9.49, p = 0.0027; Stimulated: increase from 1.15 ± 0.77 to 4.80 ± 1.26 U/mL, effect size of Cohen’s d = 13.10, p = 0.0001) in basal and stimulated saliva in T2DM rats. Further mechanistic studies revealed that BZYQF reduces glucose and lipid accumulation, enhances acetylcholine content, improves pathological lesions and inflammation, and significantly increases the expression of salivary secretion pathway signaling molecules, including PKA, IP3R, β1-AR, AQP5, CHRM3, and AMY1 in the PG and SMG of T2DM rats (p < 0.05). Conclusions: The present study demonstrated that BZYQF is able to alleviate T2DM-caused hyposalivation by improving glucose metabolism and activating the salivary secretion pathway in the PG and SMG of T2DM rats. This study might provide a novel rationale and treatment strategy for BZYQF in diabetes-induced hyposalivation in a clinical setting. Full article

Enantiopure turbo chirality in small organic molecules, without other chiral elements, is a fascinating topic that has garnered significant interest within the chemical and materials science community. However, further research into and application of this concept have been severely limited by the lack of effective asymmetric tools. To date, only a few enantiomers of turbo chiral targets have been isolated, and these were obtained through physical separation using chiral HPLC, typically on milligram scales. In this work, we report the first asymmetric approach to enantiopure turbo chirality in the absence of other chiral elements such as central and axial chirality. This is demonstrated by assembling aromatic phosphine oxides, where three propeller-like groups are anchored to a P(O) center via three axes. Asymmetric induction was successfully carried out using a chiral sulfonimine auxiliary, with absolute configurations and conformations unambiguously determined by X-ray diffraction analysis. The resulting turbo frameworks exhibit three propellers arranged in either a clockwise (P,P,P) or counterclockwise (M,M,M) configuration. In these arrangements, the bulkier sides of the aromatic rings are oriented toward the oxygen atom of the P=O bond rather than in the opposite direction. Additionally, the orientational configuration is controlled by the sulfonimine auxiliary as well, showing that one of the Naph rings is pushed away from the auxiliary group (-CH₂-NHSO₂-tBu) of the phenyl ring. Computational studies were conducted on relative energies for the rotational barriers of a turbo target along the P=O axis and the transition pathway between two enantiomers, meeting our expectations. This work is expected to have a significant impact on the fields of chemistry, biomedicine, and materials science in the future. Full article

Glioblastoma, an aggressive cancer, is difficult to treat due to its location, late detection, drug resistance, and poor absorption of chemotherapeutics. Intratumoral drug administration offers a promising potential treatment alternative with localized delivery and minimal systemic toxicity. Vanadium(V) coordination complexes, incorporating Schiff base and catecholate ligands, have shown effects as antiproliferative agents with tunable efficacy and reactivity, stability, steric bulk, hydrophobicity, uptake, and toxicity optimized for the intratumoral administration vehicle. A new series of oxovanadium(V) Schiff base–catecholate complexes were synthesized and characterized using nuclear magnetic resonance (NMR), UV-Vis, and infrared spectroscopy and mass spectrometry. Stability under physiological conditions was assessed via UV-Vis spectroscopy, and the antiproliferative activity was evaluated in T98G glioblastoma and SVG p12 normal glial cells using viability assays. The newly synthesized [VO(3-tBuHSHED)(TIPCAT)] complex was more stable (t_1/2 ~4.5 h) and had strong antiproliferative activity (IC₅₀ ~1.5 µM), comparing favorably with the current lead compound, [VO(HSHED)(DTB)]. The structural modifications enhanced stability, hydrophobicity, and steric bulk through substitution with iso-propyl and tert-butyl groups. The improved properties were attributed to steric hindrance associated with the new Schiff base and catecholato ligands, as well as the formation of non-toxic byproducts upon degradation. The [VO(3-tBuHSHED)(TIPCAT)] complex emerges as a promising candidate for glioblastoma therapy by demonstrating enhanced stability and a greater selectivity, which highlights the role of strategic ligand design in developing localized therapies for the treatment of resistant cancers. In reporting the new class of compounds effective against T98G glioblastoma cells, we describe the generally desirable properties that potential drugs being developed for intratumoral administration should have. Full article

Experimentally accessible stable polyhedral clusters of gallium differ from clusters of its lighter homologue boron by having sterically demanding external groups such as tBu₃Si, (Me₃Si)₃Si, (Me₃Si)₃C, (Me₃Si)₂N, and fluorenyl. This restricts closo deltahedral [Ga_nR_n]^z gallane chemistry to octahedral derivatives such as Ga₆R₆²⁻ (R = SiBuPh₂, SiBu^t₃) and Ga₆R₆ (R = SiMe(SiMe₃)₂) in which the bulky external silyl groups are spread out because of the relatively high local curvature of the degree 4 vertices of the central Ga₆ octahedron. The structures of larger gallium clusters are based on alternatives to closo deltahedra having exclusively high local curvature degree 4 vertices such as the 8-vertex square antiprismatic Ga₈R₈ (R = fluorenyl) or, more commonly, larger polyhedra or fused polyhedra with some bare gallium vertices. Some of the larger gallium clusters can be considered to be spherically aromatic systems with closed shells according to the jellium model. Examples include [Ga₁₃(SitBu₃)₆]⁻ with 8 cluster electrons corresponding to a filled 1S²1P⁶ shell as well as [Ga@Ga₁₈{C(SiMe₃)₃}₆]⁻ with 52 cluster electrons, Ga₂₂{E(SiMe₃)₃]₈, (E = C, Si) and Ga@Ga₁₁{GaN(SiMe₃)₂}₁₁ with 58 skeletal electrons, and [Ga₂₆{Si(SiMe₃)₃}₈]²⁻ with 72 cluster electrons. The 10-vertex species Ga₁₀{Si(SiMe₃)₃}₆, [Ga₁₀(SitBu₃)₆]⁻, and Ga₁₀(SitBu₃)₆ have structures consisting of a fusion of two polyhedra sharing bare gallium vertices with skeletal electron counts, suggesting a multicenter core bond in each of the two polyhedral cavities. Full article

Objectives: New tributyltin(IV) complexes containing the carboxylate ligands 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoic acid (HL1) and 2-(4-methyl-2-oxoquinolin-1(2H)-yl)acetic acid (HL2) have been synthesized. Methods: Their structures have been determined by elemental microanalysis, FT-IR and multinuclear NMR (¹H, ¹³C and ¹¹⁹Sn) spectroscopy and X-ray diffraction study. A solution state NMR analysis reveals a four-coordinated tributyltin(IV) complex in non-polar solvents, while an X-Ray crystallographic analysis confirms a five-coordinated trigonal-bipyramidal geometry around the tin atom due to the formation of 1D chains. A theoretical structural analysis was performed by optimization employing B3LYP-D3BJ functional and 6-311++G(d,p)/def2-TZVP(Sn) basis sets for H, C, N, O/Sn, respectively. The interactions between tin(IV) and surrounding atoms were examined by QTAIM approach. The in vitro antiproliferative activity of the synthesized compounds was evaluated by MTT and CV assays versus MCF-7 (human breast adenocarcinoma), HCT116 (human colorectal carcinoma), A375 (human melanoma), 4T1 (mouse breast carcinoma), CT26 (mouse colon carcinoma) and B16 (mouse melanoma) tumor cell lines. Results: Both synthesized compounds (nBu₃SnL1 and nBu₃SnL2) exerted powerful micromolar IC₅₀ cytotoxicity values and demonstrated high selectivity toward malignant cells. Both experimental drugs affected cell adhesion and induced anchorage independent apoptosis, a favorable type of cell death with an essential role in cancer dissemination prevention. The BSA-binding affinity of the obtained organotin compounds was followed by spectrofluorometric titration and molecular docking simulations. Conclusions: The tributyltin(IV) compounds selectively induce anoikis-like cell death in A375 cells, also highlighting the importance of the organic moiety on the tin(IV) ion in the mechanism of action. Full article

Leptin (LEP), a protein hormone well-known for its role in metabolic regulation, has recently been linked to lipid metabolism in cattle. However, its function in buffalo mammary glands remains unclear. To address this issue, we isolated and identified the LEP gene and conducted experiments to investigate its function in buffalo mammary epithelial cells (BuMECs). In this study, two transcript variants of LEP, designated as LEP_X1 and LEP_X2, were identified. The coding sequences (CDS) of LEP_X1 and LEP_X2 are 504 bp and 579 bp in length, encoding 167 and 192 amino acid residues, respectively. Bioinformatics analysis revealed that LEP_X2 is a hydrophobic protein with an isoelectric point below 7 and contains a signal peptide, while LEP_X1 is hydrophilic and lacks a signal peptide. Our study found that LEP gene expression in lactating BuMECs was significantly higher than in non-lactating cells, with LEP_X2 expression remarkably higher than LEP_X1 in lactating BuMECs. Overexpression of both LEP_X1 and LEP_X2 significantly promoted the expression of genes related to milk fat synthesis in lactating BuMECs, including STAT3, PI3K, mTOR, SCD, and SREBF1, accompanied by an increase in cellular triglycerides (TG). Interestingly, LEP_X2 overexpression significantly suppressed LEP_X1 expression while increasing intracellular TG concentration by 12.10-fold compared to LEP_X1 overexpression, suggesting an antagonistic relationship between the two variants and supposing LEP_X2 plays a dominant role in milk fat synthesis in lactating BuMECs. Additionally, four nucleotide substitutions were identified in the buffalo LEP CDS, including a nonsynonymous substitution c.148C>T (p.Arg50Cys), which was predicted to decrease the stability of the LEP protein without affecting its function. These results collectively underscore the significant role of LEP in milk fat synthesis and can provide a basis for molecular breeding strategies of buffalo. Full article

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)_n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)_n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum stability at N/P ≥ 40. The synthesized conjugates, with a diameter of <100 nm, formed nano-complexes with siRNA and exhibited a stable range of zeta potential values (13–18 mV at N/P = 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of a successful cellular internalization of siRNA. The peptides oleyl-(WRH)₃ and oleyl-(WRH)₄ showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)₄ demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells. Full article

Bufaviruses (BuV) are members of the Parvoviridae of the Protoparvovirus genus. They are non-enveloped, T = 1 icosahedral ssDNA viruses isolated from patients exhibiting acute diarrhea. The lack of treatment options and a limited understanding of their disease mechanisms require studying these viruses on a molecular and structural level. In the present study, we utilize glycan arrays and cell binding assays to demonstrate that BuV1 capsid binds terminal sialic acid (SIA) glycans. Furthermore, using cryo-electron microscopy (cryo-EM), SIA is shown to bind on the 2/5-fold wall of the capsid surface. Interestingly, the capsid residues stabilizing SIA binding are conserved in all human BuVs identified to date. Additionally, biophysical assays illustrate BuV1 capsid stabilization during endo–lysosomal (pH 7.4–pH 4) trafficking and capsid destabilization at pH 3 and less, which correspond to the pH of the stomach. Hence, we determined the cryo-EM structures of BuV1 capsids at pH 7.4, 4.0, and 2.6 to 2.8 Å, 3.2 Å, and 2.7 Å, respectively. These structures reveal capsid structural rearrangements during endo–lysosomal escape and provide a potential mechanism for this process. The structural insights gained from this study will add to the general knowledge of human pathogenic parvoviruses. Furthermore, the identification of the conserved SIA receptor binding site among BuVs provides a possible targetable surface-accessible pocket for the design of small molecules to be developed as anti-virals for these viruses. Full article

Manganese porphyrins reportedly exhibit synergic effects when combined with irradiation. However, an in-depth understanding of intratumoral heterogeneity and immune pathways, as affected by Mn porphyrins, remains limited. Here, we explored the mechanisms underlying immunomodulation of a clinical candidate, MnTnBuOE-2-PyP⁵⁺ (BMX-001, MnBuOE), using single-cell analysis in a murine carcinoma model. Mice bearing 4T1 tumors were divided into four groups: control, MnBuOE, radiotherapy (RT), and combined MnBuOE and radiotherapy (MnBuOE/RT). In epithelial cells, the epithelial–mesenchymal transition, TNF-α signaling via NF-кB, angiogenesis, and hypoxia-related genes were significantly downregulated in the MnBuOE/RT group compared with the RT group. All subtypes of cancer-associated fibroblasts (CAFs) were clearly reduced in MnBuOE and MnBuOE/RT. Inhibitory receptor–ligand interactions, in which epithelial cells and CAFs interacted with CD8+ T cells, were significantly lower in the MnBuOE/RT group than in the RT group. Trajectory analysis showed that dendritic cells maturation-associated markers were increased in MnBuOE/RT. M1 macrophages were significantly increased in the MnBuOE/RT group compared with the RT group, whereas myeloid-derived suppressor cells were decreased. CellChat analysis showed that the number of cell–cell communications was the lowest in the MnBuOE/RT group. Our study is the first to provide evidence for the combined radiotherapy with a novel Mn porphyrin clinical candidate, BMX-001, from the perspective of each cell type within the tumor microenvironment. Full article

Herbs and agro-food wastes are rich sources of bioactive compounds vital for organisms and valuable for many fields of industry. Therefore, in this study, green deep eutectic solvents (DESs) such as choline chloride/citric acid (ChCl:CitA), glucose/citric acid (Gu:CitA), glucose/urea (Gu:U), betaine/citric acid (B:CitA), and betaine/urea (B:U) at a molar ratio of 1:1 for ultrasound-assisted extraction (UAE) of antioxidants from four herbs (chamomile—Cha, lemon balm—LB, mint—M, and nettle—N) and two agro-food wastes (buckwheat husk—BH and chokeberry pomace—ChoP) were proposed. The antioxidant capacity (AC) of the obtained extracts was evaluated utilizing three antioxidant assays: cupric reducing antioxidant capacity (CUPRAC = 0.0–429.9 μmol of Trolox (TE)/g); 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS = 0.0–146.5 μmol TE/g); and 2,2-diphenyl-1-picrylhydrazyl (DPPH = 11.9–170.3 μmol TE/g). The LB extracts revealed the highest CUPRAC (59.3–429.9 μmol TE/g), ABTS (30.7–144.3 μmol TE/g), and DPPH (32.6–170.3 μmol TE/g) values. Due to the lowest antioxidant potential of LB extracts prepared using ChCl:CitA (AC = 30.7–59.3 μmol TE/g) and the highest AC demonstrated by extracts based on B:U (AC = 144.3–429.9 μmol TE/g), the UAE conditions using a new DES consisting of ChCl and U were optimized by the Box–Behnken design (BBD). Effects of three independent variables, molar ratios of the ChCl and U (mol/mol), water content (%), and sonication time (t) on the AC of LB extracts were studied by response surface methodology (RSM). The results of principal component analysis (PCA) and hierarchical cluster analysis (HCA) demonstrated that different DESs had great differences in the extraction of antioxidant compounds from herbs and agro-food residues. Full article

The reaction of the dianionic species [Fe₂(CO)₆(μ-PPh)₂]²⁻ with ^tBuN(CH₂Cl)₂ gives the di-iron carbonyl aza-diphosphido-bridged complex [Fe₂(CO)₆(µ-{P(Ph)CH₂}₂N^tBu)] (1). Attempts to prepare 1 by click-chemistry by reacting [Fe₂(CO)₆(μ-PHPh)₂] with CH₂O and ^tBuNH₂ afforded a bis-phosphido compound [Fe₂(CO)₆(µ-P(Ph)CH₂NH^tBu)₂] (2) which exists as two, syn and anti, isolable isomers depending on the relative orientation of the groups carried by the phosphorus atoms. In the presence of HBF₄.Et₂O, in dichloromethane, 1 leads to the stabilized ammonium species [Fe₂(CO)₆(µ-{P(Ph)CH₂}₂NH^tBu)](BF₄) (3). The derivatives 1–3 were characterized by IR and ¹H, ³¹P-{¹H} NMR spectroscopies. Their structures in a solid state were determined by X-ray diffraction analyses, which accord with their spectroscopic characteristics. Full article