Chemistry & Biodiversity最新文献

Four novel compounds (1–4) and 22 known compounds (5–26) were obtained from the roots of Arnebia euchroma (Royle) Johnst. The four novel compounds are three quinones named euchronins K-M (1–3), and one arnebinol compound, named arnebinol E (4). The molecular architecture of the novel compounds was unambiguously established through systematic spectral characterization, including high-resolution electrospray ionization mass spectrometry, ultraviolet, infrared, one- and two-dimensional nuclear magnetic resonance experiments, and electronic circular dichroism for stereochemical verification. Cellular bioactivity profiling of these compounds was evaluated by us in this study. In vitro cell viability screening assays, the results showed that the compounds 1, 2, 4, 10, 11, 15, 19, 20, and 26 exhibited strong neuroprotective activity, with 50% effective concentration values ranging from 3.66 to 19.23 µM.

Healing wounds may lead to significant troubles affecting human health. Hence, establishing an affordable method to speed up and improve the healing process is necessary. In this study, we report for the first time the fabrication and in vivo evaluation of sodium ampicillin (AMP)-loaded, citric-acid-cross-linked polyvinyl alcohol/dextran (CA/PVA/Dex)–electrospun nanofibers (NFs) as a multifunctional wound dressing. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA) confirmed a successful cross-linking and NF formation. An optimized CA concentration of 5.0 wt% produced uniform, bead-free nanofibrous mats with improved structural with structural integrity and sustained AMP release. The wound healing activity of the fabricated NFs was evaluated via in vivo wound healing studies and histopathological examination using a rat excision wound model. AMP-loaded CA/PVA/Dex NFs significantly enhanced wound closure, re-epithelialization, and collagen deposition compared to AMP-free NFs, with a clear dose-dependent improvement. The obtained results demonstrated that controlled local delivery of AMP through optimized CA-cross-linked PVA/Dex NFs markedly accelerates wound healing. Therefore, the developed AMP-loaded CA/PVA/Dex electrospun nanofibrous mats represent a novel, biocompatible, and effective wound dressing platform with strong potential for clinical wound management.

Type II diabetes mellites (TIIDM) characterized by hyperglycemia, insulin resistance, insensitivity, and pancreatic β-cell atrophy has gained concern due to high rise in such cases globally. This study highlighted the therapeutic potency of a novel polyherbal formulation (PHF) of Phyllanthus urinaria and Adhatoda vasica Nees mice by in vitro, in vivo, and in silico analysis in high-fat diet (HFD)–streptozotocin (STZ)-induced Swiss albino. The findings showed significant inhibition of α-amylase and α-glucosidase activity of the PHF along with decreased blood glucose level, increased glycogen and serum insulin level, elevated mRNA expression of GIPR and GLP1R, GLUT2, GLUT4, INSR, INS1, INS2, TCF7L2, and Pdx1 in both low and high dose of PHF-treated mice as compared to HFD–STZ-induced diabetic mice. Western blot results also demonstrated augmented insulin protein level in both PHF-treated groups. Okanin and vomicine, identified from LCMS analysis as potent antidiabetic bioactive compounds bind to dipeptidyl peptidase 4 (DPP4) with a binding energy of −8.04 and −7.81 kcal/mol, respectively, as compared to standard drug metformin (−5.33 kcal/mol). Inhibition of DDP-4 by bioactives of PHF aids in enhanced secretion of incretion hormones leading to insulin secretion thereby established itself as a complementary and alternative therapeutics in the management of diet-induced TIIDM.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with dysregulation of epidermal growth factor receptor (EGFR) playing a pivotal role in its pathogenesis and progression. Although EGFR-targeted tyrosine kinase inhibitors (TKIs) initially provide clinical benefits, resistance inevitably develops. Targeted protein degradation (TPD) offers a paradigm shift in cancer therapy by eliminating pathogenic proteins entirely, rather than merely inhibiting their function. This review comprehensively examines TPD strategies for lung cancer treatment, focusing on EGFR as an exemplary target. We trace the evolution of proteolysis targeting chimeras (PROTACs) from first-generation compounds to sophisticated degraders with enhanced selectivity and potency. Structural insights from AlphaFold3 predictions reveal critical EGFR features that guide rational degrader design. We systematically compare EGFR-targeting PROTACs, evaluating their degradation kinetics, mutant selectivity, and clinical potential. Beyond traditional small-molecule PROTACs, we explore emerging modalities—including peptide-based, antibody-based, and nucleic acid-based degraders—each offering unique advantages for overcoming current therapeutic limitations. We also discuss alternative TPD strategies, namely, molecular glues and lysosome-targeting chimeras (LYTACs), which expand the therapeutic arsenal against EGFR. Importantly, we identify resistance mechanisms specific to protein degraders: E3 ligase loss or mutation, EGFR alterations that disrupt ternary complex formation, deubiquitinase upregulation, and degradation pathway dysfunction. By integrating structural biology, medicinal chemistry, and clinical insights, this review provides a comprehensive roadmap for developing next-generation EGFR degraders capable of overcoming resistance and improving outcomes for lung cancer patients.

Terbinafine (Tb) is the primary commercial treatment for superficial nail infections; however, resistance is an emerging public health concern, largely driven by point mutations in the squalene epoxidase (SQLE) gene that reduce the drug's effectiveness. In this work, five novel synthetic compounds were developed and evaluated for their antifungal activity against 24 clinical isolates of Trichophyton rubrum and Trichophyton mentagrophytes. Among them, compound antifungal 2 demonstrated potent activity at the nanomolar level (ca. 73 nM), surpassing the efficacy of Tb (ca. 253 nM), and with less risk of resistance due to its rational molecular design. Molecular docking and molecular dynamics studies, conducted using a model of fungal SQLE (SE), supported the efficacy of compound 2 as a potential antifungal agent and provided reliable structure–activity relationship insights. Our results highlight the potential of combining propiolaldehyde and sulfonamide-based scaffolds to offer a promising foundation for the rational design of next-generation antifungal agents.

The current study is focused on the synthesis of a novel stimuli-responsive bio-composite hydrogel as a pH-dependent sustained-release drug delivery system (DDS). The crosslinking of chia seed glucoxylan (GX) and hydroxypropyl cellulose (HPC) with citric acid (CA) was carried out using three different concentrations of CA, that is, 1%, 5% and 10% w/v. The FTIR spectroscopy, powder x-ray diffraction (PXRD), thermogravimetric analysis (TGA) and SEM analyses confirmed the successful formation of GX–HPC–CL–CA, amorphous nature, greater stability over native GX and porous structure, respectively. Among the three formulations, the GX–HPC–CL–CA-2 (prepared from 5% CA) offered the highest swelling capacity and followed by the pattern: deionized water (DW) > pH 7.4 > pH 6.8 > pH 1.2. The GX–HPC–CL–CA-2 and GX–HPC–CL–CA-2-based tablet possessed pH-responsive swelling, salt-responsive swelling and on/off switching (swelling–deswelling) behaviour at pH 7.4/1.2, in DW/normal saline and in DW/ethanol. The theophylline release was found to be 16.8%, 92.1% and 98.3% at pH 1.2, 6.8 and 7.4, respectively, after an 8 h study, indicating a pH-dependent release, followed the first-order kinetics and a non-Fickian diffusion mechanism. The GX–HPC–CL–CA-2 appeared to be a non-thrombogenic, non-haemolytic and non-toxic material, demonstrating a haemocompatible and pH-responsive bio-composite hydrogel for developing site-specific and sustained-release DDS.

The ability of ginsenosides to regulate lipid metabolism in vivo and in vitro has been widely studied; however, the effect of panaxatriol (PT) on reducing blood lipids and its impact on intestinal microflora have not been investigated. The results of this study show that PT can not only significantly reduce the level of ALT but also effectively alleviate fatty degeneration and lipid droplet deposition in hepatocytes, thereby improving the pathological damage to the liver. It can also significantly reduce serum TC, TG, and LDL-C levels and increase HDL-C. At the same time, PT can significantly increase SOD activity, decrease MDA content, and inhibit the increase of coagulation factors such as TXB2, thus alleviating vascular endothelial injury. In addition, PT decreased the abundance of intestinal flora, increased the ratio of Firmicutes to Bacteroidetes, increased the abundance of Akkermansia, and decreased the abundance of Prevotella. Our research shows that PT can effectively alleviate the lipid metabolism disorder induced by the high-fat and high-sugar diet by improving liver lipid deposition, enhancing antioxidant capacity, regulating blood coagulation function, and reshaping intestinal flora structure, suggesting that PT has potential application value in the treatment of metabolic syndrome.

The cosmetic application of arbutin (AR) has recently been challenged due to concerns regarding the skin toxicity associated with its metabolite, hydroquinone (HQ). While the derivatization of AR provides a strategy to promote stability, the multistep and complicated chemical synthesis restricts its industrial production. The present study reported a naturally derived AR derivative, 6′-O-caffeoylarbutin (CA), which is hypothesized to resist hydrolysis to HQ owing to the conjugation effect and steric hindrance, resulting in better stability. To verify this hypothesis, the degradation of CA and AR was investigated using high-performance liquid chromatography with diode-array detection. The skin-lightening substances, AR and caffeic acid, were found in the degradation products of CA under acidic conditions, which also contained lower quantities of HQ compared to that generated by AR. However, CA was not degraded under enzymatic conditions, exhibiting better stability, which might contribute to its prolonged efficacy and reduced toxicity. The long-lasting skin-lightening efficacy of CA was further verified in a zebrafish drug-withdrawal model. Notably, Mechanistic investigations revealed that CA disrupts melanosome maturation and trafficking by modulating the melanocyte-inducing transcription factor-regulated pathway, providing molecular insights into its skin-lightening efficacy.

In the present paper, antioxidant and enzyme inhibition properties of different extracts of Crataegus monogyna were analyzed. The bioactive phytochemicals of acetone, ethanol and water extracts of C. monogyna were determined through validated LC–MS/MS method. The highest total phenolic (80.92 mg GAE/g) and flavonoid content (51.94 mg RE/g) was observed with the ethanol extract. The best antioxidant capability was observed for ethanol extract in DPPH (334.72 mg TE/g), ABTS (442.58 mg TE/g), CUPRAC (666.09 mg TE/g), FRAP (328.04 mg TE/g), and phosphomolybdenum (2.77 mmol TE/g). In addition, enzyme inhibition properties of different extracts of C. monogyna were checked for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, amylase, and glucosidase. While the most effective AChE inhibition was observed in ethanol extract (2.92 mg GALAE/g), it was noted that the most effective BChE inhibition was acetone extract (2.34 mg GALAE/g). The best tyrosinase inhibition was detected in the water extract with 79.09 mg KAE/g. The tested extracts exhibited antidiabetic potentials by amylase (0.22–0.29 mmol ACAE/g) and glucosidase inhibition (3.29–3.37 mmol ACAE/g). The chemical reactivities of the dominant molecular components in all extracts were illuminated in the light of DFT calculations and the interaction with related biological systems of these molecular structures were analyzed with the help of molecular docking analyses.

This study investigated the chemical profile and allelopathic potential of Ambrosia artemisiifolia root exudates. Metabolomic profiling was performed on hydroponic culture exudates using XAD-4 resin and UHPLC–QTOF/MS. The analysis identified a total of 1408 metabolites, with stearidonic acid (SA) being the most abundant, accounting for 28.02% of the total root exudate constituents. The allelopathic bioassays conducted on dicot and monocot weed species revealed no statistically significant increase in growth at concentrations of 10–50 µg/mL, whereas inhibition occurred at 250 µg/mL or higher. Monocots exhibited greater sensitivity to the allelopathic effects. At a concentration 500 µg/mL, the application of exudates resulted in a reduction of root and shoot lengths in Setaria viridis by 24.18% and 51.85%, respectively, and in Poa annua by 28.34% and 27.89%, respectively. SA exhibited a stronger inhibitory effect, suppressing root elongation by 43.37% and 71.66% and shoot growth by 33.51% and 64.42% in S. viridis and P. annua, respectively. Moreover, both SA and root exudates modulated superoxide dismutase (SOD) and peroxidase (POD) activities in Amaranthus retroflexus and S. viridis. At higher concentrations, growth was inhibited despite the upregulation of these antioxidant enzymes, suggesting that the accumulation of reactive oxygen species (ROS) exceeded the plants’ antioxidant capacity. Results demonstrate root exudates drive invasion by disrupting antioxidant defenses, offering potential for concentration-dependent bioherbicides in sustainable weed management.