查看更多>>摘要：Abstract A bis‐dimethylamine substituted xanthone (Xan‐2) was obtained by cationic modification of the free C3 and C6 hydroxy groups of 1,3,6‐trihydroxyxanthone (Xan‐1) which was isolated from Polygala hongkongensis Hemsl.. The results of the spectroscopic analysis, melting profiles, electrophoretic migration, PCR assay and molecular docking indicated that the hydrophobic plane of Xan‐1 and Xan‐2 could intercalate into the DNA base pairs meanwhile the basic amine alkyl chain of Xan‐2 could bind with DNA phosphate framework via electrostatic interaction. Thus, Xan‐2 exhibited higher DNA binding affinity than Xan‐1. Further study showed that Xan‐2 could inhibit the proliferation of HeLa, SGC‐7901 and A549 cells effectively by MTT assay and induce apoptosis of HeLa cells as detected by AO/EB staining and flow cytometry assay. Interestingly, Xan‐2 exhibited selective cytotoxicity to cells, which was proved by its relatively low inhibitory effect on Raw 264.7?cell. What these studies mean is that disubstituted amine alkyl chains will play an important role in DNA binding property and cytotoxic activity, providing a direction for the development of novel potential antitumor agents.
Ivan Pavlovi?Mirjana Radenkovi?Marina T. Milenkovi?Marjan Niketi?...
9页
查看更多>>摘要：Abstract Dry MeOH extract of Ferula heuffelii (Apiaceae) underground parts was tested for spasmolytic, gastroprotective and antioxidant activities. HPLC analysis revealed that chlorogenic acid (CGA; 34.6?mg/g) was its main constituent. Extract in?vitro exhibited notable total antioxidant activity (FRAP value=1.0 μmol Fe2+/mg), and scavenging of DPPH (SC50=62.5?μg/ml) and ?OH radicals (49.5?% at 20?μg/ml in 2‐deoxyribose assay). In vitro on isolated rat ileum, extract exhibited significant spasmolytic activity, i.?e., it showed 124.6?% of maximal atropine effect on spontaneous contractions (at 100?μg/ml), and reduced spasmogenic effect of KCl (80?mm) to 44.4?% (at 60?μg/ml) and of highest applied concentration of ACh to 26.3?% (at 120?μg/ml). In parallel experiments, spasmolytic effect of CGA was also demonstrated. In acute EtOH‐induced gastric ulceration model in rats, extract (100?mg/kg p.o.) showed significant gastroprotective effect (gastric damage score 0.50), similar to ranitidine (20?mg/kg p.o.). Obtained results showed that tested F. heuffelii polar extract represents new herbal preparation with potential use against some gastrointestinal complaints.
Swarnagowri NayakSantosh L. GaonkarDruti HazraKiran Chawla...
12页
查看更多>>摘要：Abstract In drug discovery, the hybridization of bioactive pharmacophores is a powerful tool for targeting enzymes involved in cancer and microbial cell growth. A combination of 1,3,4‐oxadiazole and isobenzofuran may improve the antitumor and antimicrobial properties of the hybrid molecules. A series of hybrid molecules having 1,3,4‐oxadiazole and isobenzofuran were synthesized and structural characterization was done by FT‐IR, 1H‐NMR, 13C‐NMR, and mass spectrometry. Molecular docking studies were performed to investigate binding interactions of compounds with proteins (PDB NO: 2R3J and 1GII), and the results were consistent with in?vitro anticancer data. All the synthesized compounds were tested for antimicrobial activity against S.?aureus, E.?faecalis (Gram‐positive) and E.?coli and P.?aeruginosa (Gram‐negative) bacterial strains. Among the synthesized compounds, 7a and 7b displayed good activity against the tested bacterial strains. Also, compounds were tested for their anti‐tumor activity against breast cancer (MCF‐7) and colon cancer (HCT‐116) cell lines via SRB assay. In comparison to doxorubicin (1.14?μM), hybrids 7e (4.32?μM), 7f (4.15?μM), 7g (4.66?μM), and 7h (4.83?μM) demonstrated comparable IC50 value against the HCT 116 cell line.
查看更多>>摘要：Abstract Evodileptin B (1) is a natural anthranilate derivative isolated from the ethanol extract of the aerial parts of Evodia lepta (Spreng.) Merr., a traditional medicinal plant of the family Rutaceae. We readily synthesized 1 via the amidation of phloretic with methyl anthranilate and evaluate its neuroprotective activity using a C.?elegans Parkinson's disease (PD) model. The results showed that evodilpetin B ameliorated MPP+‐induced dopaminergic (DA) neurodegeneration in a dose‐dependent manner. Evodileptin B treatment also significantly improved the DA neurotransmission‐related behavioral defects such as reduced locomotory and food‐sensing ability of worms under MPP+ exposure conditions, suggesting its potential application for the functional restoration of DA neurons. In addition, we found that 1 has an ability to regulate aggregation of α‐synuclein by increasing proteasome activity in the human α‐synuclein‐expressing mutant worms. These results demonstrate that evodileptin B has strong neuroprotective properties and may be useful in the treatment of PD.
查看更多>>摘要：Abstract Cytochrome P450 enzymes (CYPs or P450s) are ubiquitous heme‐dependent enzymes that catalyze the monooxygenation of non‐activated C?H bonds to modify the structure of the substrate. In this study, we heterologously expressed CYP107X1 from Streptomyces avermitilis and conducted in?vitro substrate screening using the alternative redox partners putidaredoxin and putidaredoxin reductase. CYP107X1 catalyzed the 16α‐hydroxylation of progesterone with regio‐ and stereoselectivity. The spectroscopic analyses showed that CYP107X1 bound progesterone with a relatively high Kd value of 65.3±38.9?μM. The Km and kcat values for progesterone were estimated to be 47.7±12.0?μM and 0.30?min?1, respectively. Furthermore, a crystal structure was obtained of CYP107X1 bound with glycerol from the buffer solution. Interestingly, a conserved threonine was replaced with asparagine in CYP107X1, indicating that it may adopt an unnatural proton transfer process and play a crucial role in its catalytic activity.
查看更多>>摘要：Abstract Penthorum chinense Pursh. is a traditional herbal medicine of Miao, and its extracts (PCPE) have been used for treatment of liver diseases in the clinic including nonalcoholic fatty liver disease (NAFLD). However, the active components and pharmacological mechanisms of PCPE for treating NAFLD remain unclear. This study aimed to explore potential mechanisms of action through network pharmacology, molecular docking combined with experimental in?vitro. A total of five dihydroflavonoids (1–5) with the same parent nucleus of pinocembrin (PCB) from PCPE, were selected as bioactive ingredients and 109 potential targets related to NAFLD were obtained from public databases and literature mining. The core targets related to the bile secretion signaling were selected based on PPI network and KEGG enrichment analysis for exploring the mechanism of PCPE against NAFLD. Molecular docking results showed good interaction between the core targets in bile secretion signaling pathway and the five compounds predicted to be bioactive. With the strong binding activity to retinoid X receptor‐alpha (RXRA) and farnesoid X receptor (FXR) protein, pinocembrin‐7‐O‐β‐D‐glucoside (PCBG, the highest content in PCPE) and its metabolite PCB, could significantly increase the expression of RXRA, FXR and bile salt export pump (BSEP) in L02 cells, and significantly decrease the expression of cholesterol 7α‐hydroxylase (CYP7A1) at mRNA and protein levels. This study provided favorable evidence for mechanism of the main dihydroflavonoids of PCPE against NAFLD, and presented a paradigm for the study of ethnomedicine.
查看更多>>摘要：Abstract To discover more effective antifungal agents, twenty N‐(1H‐pyrazol‐5‐yl)nicotinamide derivatives were designed, synthesized, and structurally confirmed by 1H‐NMR, 13C‐NMR, and ESI‐MS. All target compounds were evaluated for their antifungal activities by mycelia growth inhibition. Preliminary screening results displayed that many of these compounds had good fungicidal activity to S.?sclerotiorum and V.?mali. Compound B4 exhibited antifungal activity against S.?sclerotiorum and V.?mali with EC50 values of 10.35 and 17.01?mg/L, respectively. The experiment in?vivo identified that compound B4 was effective for suppressing rape sclerotinia rot caused by S.?sclerotiorum at 50?mg/L. The molecular docking study and scanning electron microscopy preliminary clarified the possible antifungal mechanism of compound B4.
查看更多>>摘要：Abstract Ageratum conyzoides L. (Asteraceae) possesses wound healing, antimicrobial, and anti‐inflammatory activities. Traditionally, this plant is used in skincare. The essential oil (EO) of A. conyzoides aerial parts contains the chromenes precocene I (1) and precocene II (2) as major constituents. This study evaluated precocene II (2) for its in?vivo efficacy, mechanistic analysis, and synergistic interaction with norfloxacin against methicillin‐resistant Staphylococcus aureus (MRSA). The study showed that 2 interacted synergistically (Fractional Inhibitory Concentration Index, FICI≤0.5) with norfloxacin and oxacillin and reduced their MIC values significantly. These observations were further validated using the mice model and showed a significant reduction in bacterial load at much lower doses of 2 and norfloxacin without toxicity at 200?mg/kg body weight. Mechanistic studies revealed that 2 regulates bacterial resistance against clinical isolates of S. aureus through membrane disturbance in a dose‐ and time‐dependent manner. Further, precocene II (2) damaged the membrane of the bacteria, as observed from the increased membrane depolarization and uptake of propidium iodide. It also displayed high selectivity towards S. aureus over mammalian cell lines. The in?vitro results highlighted the synergistic activity of 2 through the cell membrane damage without any detrimental effect on mammalian cells. In vivo results showed that 2 in combination with norfloxacin significantly reduced bacterial load at much lower concentrations through synergistic interaction without apparent toxicity.
查看更多>>摘要：Abstract Seven new labdane diterpenoids, hypopurolides A–G (1–7) were discovered from the aerial part of Hypoestes purpurea, along with one known analog, hypopurin D (8). The structures of 1–7 were characterized based on 1H‐, 13C‐, and 2D‐NMR, and HR‐ESI‐MS spectra. The absolute configurations of 1–7 were defined by single‐crystal X‐ray diffraction and electronic circular dichroism (ECD) data. Compounds 1–8 were tested for their nitric oxide (NO) inhibitory and cytotoxic effects. Compound 6 displayed moderate inhibitory effect toward LPS‐induced NO release in RAW 264.7 cells with an IC50 value of 41.50?μM.
NSTL
Wiley