Chemistry & Biodiversity最新文献

Ziziphora tenuior is a herb known for its potent pharmaceutical activities. However, the specific compounds of the flowers of this herb have not been fully studied yet. This study used GC-MS to conduct a chemical analysis of the methanol and dichloromethane extracts of Z. tenuior flowers. Additionally, it sought to assess the potential antibacterial activity of the extracts against vancomycin-resistant enterococci (VRE) bacteria by predicting the interactions between one of the most prevalent compounds in the extracts and the D-alanyl-D-lactate ligase (VanA) protein, which is responsible for enterococci resistant to vancomycin. The results revealed a total of 15 compounds in the methanolic extract and 12 compounds in the dichloromethane extract. Among these, 5-methyl-2-(1-methylethylidene)-cyclohexanone, also known as pulegone, constituting 52.6 % of the methanolic extract and 34.6 % of the dichloromethane extract, was the most abundant compound in the extracts. Furthermore, the in-silico analysis demonstrated that pulegone exhibited significant interactions with VanA, as indicated by docking energy values of -7 kcal/mol and the formation of one hydrogen bond. The study suggests that pulegone shows promise as an antibacterial agent against VRE by potentially interacting with VanA protein and serving as a key inhibitor in fighting vancomycin resistance.

Peptides containing the sequences 20RRWQWR25 and 20RRWQWRMKKLG30 derived from Bovine lactoferricin (LfcinB) were synthesized and their antibacterial effect against reference strains and sensitive and resistant clinical isolates of E. coli was evaluated. Tetra-branched multiple antigen peptide (MAP) ((RRWQWR)2-K-Ahx-C)2 exhibited significant antibacterial activity against sensitive, resistant, and multidrug-resistant clinical isolates of E. coli. Peptide 3: RRWQWR-Nal-KKLG; MIC=16 µM, 26[F]: (RRWQWRFKKLG)2-K-Ahx; MIC=15 µM, 17: (RRWQWRFK)2-K-Ahx; MIC=9 µM, and LfcinB (20-25)2: (RRWQWR)2-K-Ahx; MIC=11 µM exhibited the highest antibacterial activity against E. coli strains, with bactericidal effect and haemolytic effect at MIC less than 5% and a therapeutic index >1. A synergistic effect of peptides 26[F] and 17 with ciprofloxacin (CIP) or ceftriaxone (CEF) was observed. Prolonged treatment of E. coli ATCC 25922 with sublethal concentrations of CIP induced resistance in this strain, whereas some peptides did not induce resistance. These peptides can be considered to be promising candidates for treating infections caused by resistant strains of E. coli.

Vascular dementia (VaD) is a neurodegenerative disease resulting from cerebral vascular obstruction, leading to cognitive impairment, and currently lacks effective treatment options. Due to its complex pathogenesis, multi-target drug design (MTDLs) strategies are considered among the most promising therapeutic approaches. In this study, we designed and synthesized a series of novel indanone derivatives targeting targets related to vascular health and dementia. The results indicated that compound C5 exhibited excellent acetylcholinesterase inhibitory activity (IC50 = 1.16 ± 0.41 μM) and anti-platelet aggregation activity (IC50 = 4.92 ± 0.10 μM) within ranges of 0.1-1000 μM and 0.03-300 μM, respectively, possibly mediated by molecular docking interactions. Furthermore, compound C5 demonstrated protective effects on cells at concentrations ≤50 μM, significantly reducing the release of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) in a concentration-dependent manner, showcasing its potent neuroinflammatory inhibitory effects. Anti-inflammatory therapies are regarded as effective strategies for treating VaD. Therefore, compound C5 holds promise as a novel candidate drug for further investigation into the treatment of vascular dementia.

In light of antibiotics being classified as environmental hormone-like compounds, their interference with the endocrine system has significantly impacted human health and ecological environments. This study employed Gaussian09 software's Density Functional Theory (DFT) to structurally optimize and perform frequency calculations on 23 representative antibiotic molecules, aiming to obtain microscopic quantum mechanical structural parameters.Physicochemical property parameters were acquired through the RDKit database in the ChemDes platform. Through multiple linear regression analysis, the primary factors affecting antibiotic biotoxicity (pLD50) were identified, leading to the establishment of a QSAR model. The predictive capability of the model was analyzed using leave-one-out cross-validation, and molecular docking was used to investigate the binding mode and mechanism of action between estrogen receptors (ER) and antibiotics. Research outcomes indicate that the established QSAR model C has regression coefficients R2 and leave-one-out cross-validation coefficients Q2 of 0.92474 and 0.74913, respectively, demonstrating good stability and predictive power. Analysis through molecular surface electrostatic potential, frontier molecular orbitals, molecular docking, and molecular dynamics revealed that the potential estrogenic disrupting effects are primarily due to hydrogen bonds and hydrophobic interactions between antibiotics and estrogen receptors. This provides a valuable exploration for identifying and screening PPCPs with potential estrogenic disrupting effects.

Diffuse large B cell lymphoma (DLBCL) is classified into Germinal Center B-cell (GCB) and activated B-cell (ABC) subgroups originating from different stages of lymphoid differentiation. Cell of origin dictates the behavior and therapeutic response of DLBCL. This study aimed to evaluate single and combinatorial effects of metformin and thymoquinone (TQ) in two DLBCL cell lines belonging to GCB and ABC subtypes. Metformin and TQ caused dose-dependent responses in both ABC and GCB DLBCL subtypes. Metformin had a greater impact on the ABC subtype while TQ demonstrated more pronounced effects on the GCB subtype. Synergistic effects were observed in the DHL4 (GCB subtype) but not in the HBL1 (ABC subtype) cell line. This is the first study to compare the effects of metformin and TQ in ABC versus GCB subtype of DLBCL. It brings valuable results that could be utilized in further research aimed at reshaping treatments for subtype-specific lymphomas.

In the fight against pathogenic infections, antimicrobial peptides (AMPs) constitute a novel and promising class of compounds that defies accepted drug development conventions like Lipinski's rule. AMPs, often known as nature's antibiotics, are remarkably effective against a variety of pathogens, including viruses, bacteria, parasites, and fungi. Their effectiveness, despite differing from traditional drug-like properties defies accepted standards. This review investigates the complex world of AMPs with an emphasis on their structural and physicochemical properties, which include size, sequence, structure, charge, and half-life. These distinguishing characteristics set AMPs apart from medications that adhere to Lipinski's rules and greatly contribute to their selective targeting, reduction of resistance, multifunctionality, and broad-spectrum efficacy.

Plantago is a large genus under family Plantaginaceae. Plantago species were noted for potent antioxidant, anti-inflammatory and wound healing activities. The current research investigated the potential bioactivities as the metabolic content of Plantagoboisserei extract. Results highlighted the rich content of phenolics (450.93 ± 7.4 mg GAE/g extract) and flavonoids (144.2 ± 3.6 mg RE/g extract). HPLC analysis enabled the detection of 17 phenolic constituents among which ellagic acid was found in highest concentration followed by rutin. P. boisserei exhibited a potent antioxidant activity evidenced by the IC50 values in ABTS and H2O2 assays (10.95 and 10.87 µg/mL, respectively) as well as in TAC assay (67.94 mg AAE/g). The anti-microbial activities revealed a moderate activity against Staphylococcus aureus and Proteus vulgaris. In vitro anti-inflammatory potential indicated a characteristic inhibition against COX-1 and COX-2 enzymes with IC50 62.8 and 14.23 µg/mL, respectively, compared to ibuprofen (IC50 8.07 and 6.58, respectively). Additionally, P. boisserei extract achieved a potent wound healing activity using in vivo rat model, this might be attributed to its high content of flavonoids together with other polyphenolic compounds that have a great free radical scavenging potential. P. boisserei is a promising candidate for more extensive phytochemical and biological exploration.

Fusarium verticillioides is a prevalent plant pathogenic fungus known to produce harmful mycotoxins, including fumonisins and emerging toxins. This study aimed to investigate the influence of substrate on the temporal patterns of mycotoxin biosynthesis by F. verticillioides, employing a combined OSMAC (One Strain-Many Compounds) strategy and metabolomics approach. The fungus was cultured under various media conditions, and samples were collected over time. LC-MS/MS analyses and a dereplicative workflow were used to profile the secondary metabolite production, focusing on mycotoxins. The results demonstrated that modifying the culture conditions led to significant variations in fungal growth and the nature and relative concentrations of mycotoxins produced. Corn meal agar (CMA) medium was favorable for fumonisins A₁ and B₁, while malt extract agar (MEA) favored fumonisins A₂ and B₂. The study also identified the production of other mycotoxins related compounds as fusarins, bikaverin derivatives and fumonisins analogs, under different growth conditions. This study highlights the potential of combining OSMAC and metabolomics to unravel the substrate-dependent and time-dependent variations in mycotoxin biosynthesis by F. verticillioides. The insights gained provide a better understanding of the ecophysiology of this fungus and the occurrence of its mycotoxins, which can inform targeted mitigation strategies to ensure food and feed safety.

Lotustine A (1), an undescribed C-₁₃ norisoprenoid, along with 22 known analogues and two eudesmanoids, were isolated from the aerial parts of Nelumbo nucifera Gaertn. Among them, compounds 2, 15, 17, 21, 22, 24, 25 were isolated from N. nucifera leaves for the first time. Their structures, including absolute configurations, were elucidated by nuclear magnetic resonance, mass spectroscopy, and the modified Mosher's method. Compound 1 is the first example of C-₁₃ norisoprenoid with a terminal double bond between C-5 and C-13. Moreover, the lipid-lowering activities of the isolates were evaluated, and the results showed that 2, 24 and 25 could remarkably decrease the levels of both total cholesterol and triglyceride in free fatty acids induced HepG2 cells at the concentration of 20 μM. The oil red staining assay further demonstrated the lipid-lowering effects of 2, 24 and 25. The western blot results indicated that compounds 2, 24 and 25 could regulate the lipid metabolism via the activation of the AMPK/ACC/SREBP-1c signaling pathway.

The study aimed to assess the antioxidant and anti-inflammatory activities of polyphenol-rich extracts of seedless variety of Ziziphus mauritiana (SZM). Reverse Phase High Performance Liquid Chromatography analysis of SZM leaves and fruit extracts in ethanol revealed the presence of sixteen phenolics including chlorogenic acid, p-coumeric acid, gallic acid, kaempferol and rutin. Leaf extract showed higher total phenolic and total flavonoid contents (177.6 mg/100 g and 46.2 mg/100 g) than in fruit extract (137.8 mg/100 g and 14.1 mg/100 g). The leaf extract exhibited higher DPPH radical-scavenging activity (63.5%) than the fruit extract (58.2%). The anti-inflammatory activity was evaluated on carrageenan-induced rat model and suppression of inflammatory biomarkers (Interleukin-6, Tumor necrosis factor-α and CRP) were studied.  The fruit extract exhibited inhibition (98.1%) at the dose of 500 mg/kg body weight (BW), comparable to the indomethacin (98.4%). Both extracts suppressed the inflammatory biomarkers, but pronounced results showed by the fruit extract including CRP, IL-6, and TNF-α. The leaf extract demonstrated the higher antioxidant potential as evident from the superoxide dismutase, catalase, malondialdehyde, glutathione peroxidase and glutathione levels. These findings suggest that SZM leaf and fruit extracts possess potential antioxidant and anti-inflammatory properties and can play a significant role in mitigating oxidative stress.