Chemistry & Biodiversity最新文献

Breast cancer remains one of the leading causes of cancer-related mortality in women, emphasizing the urgent need for safer and more effective therapeutic agents. Natural phytochemicals, due to their structural diversity and pharmacological potential, are increasingly recognized as promising candidates in anticancer research. In this study, the anticancer activity of the n-hexane extract from Gmelina arborea leaves was evaluated through a multidisciplinary approach involving LC-MS/MS analysis, molecular docking, molecular dynamics (MD) simulation, and in vitro cytotoxicity assays. LC-MS/MS profiling identified 83 phytochemicals based on accurate mass measurements and fragmentation patterns. Among them, hesperetin-3',5,7-tri-glucuronide, emerged as a key compound due to its potential interaction with the epidermal growth factor receptor (EGFR). Molecular docking studies using EGFR crystal structures (1M17 and 1IVO) revealed strong binding affinities of -9.122 and -7.246 kJ/mol, respectively. MD simulations further validated the complex stability for compound 77. Additionally, the extract demonstrated cytotoxic activity against MCF-7, HepG2, and HEK-293 cell lines, with the strongest activity observed in MCF-7 breast cancer cells. These findings were further supported with a clonogenic assay on MCF-7 cells using IC₅₀ concentration. Overall, the findings highlight Gmelina arborea as a promising source of anticancer agents.

Ligusticum chuanxiong Hort. (CX), a traditional herbal plant, has demonstrated significant therapeutic potential for treating neurological disorders. However, systematic studies screening its key active compounds for Parkinson's disease (PD) have been limited. This study aims to comprehensively identify the primary anti-PD compounds derived from CX by integrating computational and experimental approaches, including network pharmacology, HPLC analysis, spectrum-effect relationships, and molecular docking, alongside cellular and animal model validation. Our findings indicate that among the three CX extracts tested, CXEO (essential oil of CX) exhibited the most potent anti-PD activity. Spectrum-effect relationship analysis, validated through experimental studies, identified Senkyunolide A as the key active compound in CXEO. Network pharmacology analysis, further supported by validation using the GEO database, revealed tumor necrosis factor (TNF), interleukin 1β (IL-1β), intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule-1 (VCAM1), and prostaglandin endoperoxide synthase 2 (PTGS2) as the primary molecular targets through which Senkyunolide A exerts its anti-PD effects, suggesting that its mechanism of action may involve modulation of inflammatory pathways. Additional investigation into differentially expressed genes related to PD, based on the GEO database, further confirmed the clinical relevance of Senkyunolide A in PD. These findings suggest that Senkyunolide A from L. chuanxiong Hort. holds potential as a therapeutic compound for PD.

In this study, novel di- and tetrapropargyl derivatives of (+)-catechin were synthesized and characterized using IR, ¹H and ¹³C{¹H} NMR, as well as LC-MS. Furthermore, the ground-state geometries of compounds 1 and 3 were optimized using DFT calculations at the B3LYP/6-31G(d) level. These optimizations allowed the identification of key bond length and angle variations. Tetrapropargyl-catechin (3) shows a significantly higher antiplasmodial activity than dipropagyl-catechin (1), with IC₅₀ values of 4.70 µg/mL and 20.22 µg/mL, respectively. Notably, 1 demonstrated low toxicity (IC₅₀ > 100 µg/mL), while 3 showed higher toxicity (IC₅₀ = 7.1 µg/mL). Complementary in silico molecular docking studies were conducted using the PfAMA1 protein (PDB: 3SRJ), a crucial receptor involved in parasite-host cell interaction. Both compounds demonstrated favorable binding profiles, with 3 achieving the best docking score (E = -7.4 kcal/mol), in agreement with the in vitro results. Computational analyses, including HOMO-LUMO and molecular electrostatic-potential mapping (MEP), revealed insights into the compounds' electronic properties and potential for further functionalization. The introduction of multiple propargylic groups in 3 enhanced π-delocalization, thus potentially increasing its binding affinity, while it may also be associated with higher cytotoxicity. These findings highlight the promising antimalarial potential of propargylated catechin derivatives, particularly dipropargyl-catechin (1), for the favorable cytotoxicity profile, for future antimalarial drug development.

This study investigates the efficacy of natural date stem powder (NDSP) as an economical and environmentally sustainable adsorbent for the removal of crystal violet dye from wastewater. Thorough characterization using SEM, FTIR, and XRD elucidated NDSP's structural and functional attributes favorable for dye adsorption. A systematic evaluation of critical parameters such as initial dye concentration (1-10 mg/L), adsorbent dosage (0.5-3 g/L), contact period (0-120 min), stirring speed (0-700 rpm), and ionic additives was investigated to determine optimal conditions for maximum removal efficiency. The equilibrium values conform most closely to the Langmuir isotherm model (R² = 0.78), signifying monolayer adsorption with a maximum capacity of 9.47 mg/g. Kinetic analyses demonstrated a strong connection with the Elovich model (R² = 0.982), affirming chemisorption as the primary process. Thermodynamic analysis indicated a spontaneous process (ΔG° = -5.72 to -6.83 kJ/mol) and an endothermic reaction (ΔH° = 7.36 kJ/mol). These findings establish NDSP as a viable, sustainable option for wastewater treatment, integrating agricultural waste valorization with efficient dye elimination.

Three previously undescribed compounds (1-3), including an unusual pyridazine derivative, one sesquiterpenoid, and a polyketide with novel stereochemistry, together with 24 known compounds (4-27), were isolated from the deep-sea-derived Penicillium limosum ZEN48. The structures of the new compounds were elucidated by comprehensive analyses of one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, and optical rotation calculation. Compounds 13, 18, and 19 exhibited considerable inhibitory effect in osteoclast formation at 20 µM in bone marrow-derived monocytes, indicating their potential application in anti-osteoporotic therapy.

This study evaluated the cardioprotective potential of Vitex simplicifolia methanol extract (VSME) and explored its underlying mechanisms of action. Twenty-five male rats were assigned to five groups (n = 5). Group 1 served as the normal control, while groups 2-5 were exposed to 5 mg/kg body weight of cadmium chloride (CdCl₂) daily. Group 2 received no treatment, whereas groups 3 and 4 were treated with 200 and 400 mg/kg VSME, respectively, and group 5 received 10 mg/kg propranolol (standard drug), all for 21 days via oral administration. Biochemical and histopathological analyses of the heart were conducted post-treatment. Cadmium exposure significantly elevated cardiac malondialdehyde, triglycerides, cholesterol, low-density lipoprotein, creatine kinase, lactate dehydrogenase, and C-reactive protein, while reducing high-density lipoprotein, superoxide dismutase (SOD), catalase, and glutathione peroxidase. VSME treatment reversed these changes, restoring antioxidant status, lipid profile, cardiac biomarkers, and myocardial architecture. Molecular docking revealed strong binding affinities of VSME phytochemicals (kaempferol, isorhamnetin, luteolin) with Kelch-like ECH-associated protein 1 (Keap1), primarily through hydrogen bonds. These compounds exhibited superior drug-likeness, pharmacokinetics, and safety profiles compared to the standard Keap1 inhibitor, CPUY192018. These findings suggest that VSME may exert cardioprotective effects partly through antioxidant activity and potential interference with the Keap1-Nrf2 interaction, as supported by molecular docking.

Diabetes is a complex and refractory metabolic disease severely threatening human health. A common feature of both type 1 and advanced type 2 diabetes is the failure and loss of functional β-cells. Stimulating pancreatic β cell proliferation for endogenous regeneration represents the most direct therapeutic approach.Through screening of secondary metabolites from the endophytic fungus of Ajuga decumbens Thunb using a zebrafish model, we identified Arenarine D promoting β cell regeneration. In a low-dose STZ-induced T1DM mouse model, Arenarine D treatment lowered blood glucose and improved insulin resistance. Importantly, we found it promotes mouse β cell proliferation by inhibiting DYRK1A. To our knowledge, we are the first to report that Arenarine D can promote the proliferation of pancreatic β cells by inhibiting DYRK1A, and this effect stems from the replication of existing β cells rather than other pathways. This demonstrates the great potential of Arenarine D in the treatment of T1DM.

In line with the need for new candidate molecules in cancer treatment, 2-substituted benzothiazole derivatives were synthesized in this study, their antiproliferative activities were evaluated, and their potential was investigated through ADMET, DFT, and molecular docking studies. During the synthesis process, 7-arylidinobicyclo[3.2.0]heptan-6-one intermediates were reacted with 2-amino-benzenethiol in the presence of p-toluenesulfonic acid under reflux conditions to obtain the target 2-((1S,2S)-2-((E)-substituestyryl)cyclopentyl)benzo[d]thiazole derivatives. The structures were confirmed by NMR and IR spectroscopy. The antiproliferative effects of the compounds were evaluated using the BrdU test in C6 and HeLa cell lines. In the cytotoxicity test, compounds 16 and 20 showed the highest cytotoxicity against C6 cells (IC₅₀: 28.68 and 26.39 µM). Against HeLa cells, compounds 14, 16, and 19 showed notable activity (IC₅₀: < 5, 22.83, and 15.82 µM, respectively). DFT calculations (B3LYP/6-31G+(d,p)) showed strong agreement with experimental NMR data. MEP maps were generated for compounds 14-20, and potential regions contributing to biological activity were analyzed. ADMET analysis indicated that the compounds have suitable pharmacokinetic and oral bioavailability profiles. Molecular docking showed that compound 17 has strong interactions with the target proteins (PDB: 1M17 for HeLa and PDB: 1JQH for C6). In conclusion, compounds 14-20 emerge as potential candidates in anticancer drug development processes.

This study aimed to valorize galgal (Citrus pseudolimon L.) peel waste by extracting and microencapsulating its essential oil (EO) for potential food applications. The EO yield was 3.5%, with D-limonene (42.94%) as the major compound. Emulsions were prepared using maltodextrin/gum Arabic in varying ratios with soy lecithin as an emulsifier. The most stable emulsion, based on creaming index, was spray-dried to obtain microcapsules. The powder exhibited 2.52% moisture, 0.243 water activity, 19.78% total oil, and 90.23% encapsulation efficiency. It showed strong antioxidant activity (85.23% DPPH inhibition) and antibacterial activity against S. aureus and E. coli (zones of inhibition: 24.47 mm and 23.75 mm). Particle size ranged from 1-100 µm, with a zeta potential of -15.9 mV, and FE-SEM confirmed uniform morphology. Among LDPE-packed samples, room temperature storage maintained better stability. The study demonstrates that microencapsulated galgal EO offers promising antioxidant and antimicrobial properties for food preservation.

Continuing our research on food chemistry, we focus on the genus Allium, globally consumed for its flavor, organoleptic properties, and health benefits. These spices produce secondary metabolites with various biological activities, such as cardiotonic, antioxidant, antimicrobial, antiparasitic, and anticarcinogenic effects. We chemically investigated Eurasian wild Allium species: A. schoenoprasum L. (ASCL), A. strictum Schrad (ASTL), and A. splendens Wild. ex Schult (ASWS) using UHPLC/MS analysis, along with assessments of their total polyphenol content, total flavonoid content (TFC), and total tannins content (TTC) via Folin-Ciocalteu, aluminum chloride, and vanillin methods. Antioxidant capacities were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and FRAP assays. Results showed similar total polyphenol content, TFC, and TTC values for ASTL and ASCL, supporting the UHPLC/MS findings. Both ASTL and ASCL exhibited promising antioxidant potential, with RSa₅₀ and RC₅₀ values comparing favorably to vitamin C. Additionally, they showed antibacterial and antifungal activities against multiple strains, with MICs ranging from 15.625 to 31.25 µg/mL. Given their edibility, these species may serve as potential active ingredients in nutraceuticals and food supplements targeting oxidative stress and microbial diseases.