Toward the search of new antibacterial agents to control methicillin-resistant Staphylococcus aureus (MRSA), a class of new norfloxacin-1,3,4-oxadiazole hybrids were designed and synthesized. ...Antibacterial activities against drug-sensitive bacteria S. aureus and clinical drug resistant isolates of MRSA were evaluated. Compound 5k exhibited excellent antibacterial activities against S. aureus (MIC: 2 μg/mL) and MRSA1–3 (MIC: 0.25–1 μg/mL). The time-kill kinetics demonstrated that compound 5k had an advantage over commonly used antibiotics vancomycin in killing S. aureus and MRSA. Moreover, compound 5k could inhibit the bacteria and destroy their membranes in a short time, and showed very low cytotoxicity to NRK-52E cells. Some interesting structure-activity relationships (SARs) were also discussed. These results indicated that these norfloxacin-1,3,4-oxadiazole hybrids could be further developed into new antibacterial agents against MRSA.
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Previous studies supposed that Amadori rearrangement products (ARPs) of peptides might have better umami-enhancing abilities. To confirm this, five ARPs (EP-ARP, AH-ARP, EE-ARP, β-AH-ARP, ...RFPHADF-ARP) were synthesized using a food-grade preparation method, and their chemical structures were clearly demonstrated by mass spectrometry and 1D/2D NMR. Sensory experiments showed that ARPs had better umami-enhancing abilities than the corresponding peptides in this research, though their enhancing performance varied. ARPs showed a synergistic effect with multiple umami substances (MSG and GMP), while their corresponding peptides did not. RFPHADF-ARP had good umami-enhancing capacity, despite that RFPHADF was a bitter peptide without any umami/umami-enhancing property. RFPHADF-ARP could bind to the T1R3, which is beneficial to the stability of the active conformation of the umami receptor. The introduction of glucose via the Maillard reaction increased the binding force of RFPHADF with the umami receptor by influencing the electron density distribution and offering more binding groups (hydroxide group).
To improve the insecticidal activity of (+)-nootkatone, a series of 42 (+)-nootkatone thioethers containing 1,3,4-oxadiazole/thiadiazole moieties were prepared to evaluate their insecticidal ...activities against Mythimna separata Walker, Myzus persicae Sulzer, and Plutella xylostella Linnaeus. Insecticidal evaluation revealed that most of the title derivatives exhibited more potent insecticidal activities than the precursor (+)-nootkatone after the introduction of 1,3,4-oxadiazole/thiadiazole on (+)-nootkatone. Among all of the (+)-nootkatone derivatives, compound 8c (1 mg/mL) exhibited the best growth inhibitory (GI) activity against M. separata with a final corrected mortality rate (CMR) of 71.4%, which was 1.54- and 1.43-fold that of (+)-nootkatone and toosendanin, respectively; 8c also displayed the most potent aphicidal activity against M. persicae with an LD50 value of 0.030 μg/larvae, which was closer to that of the commercial insecticidal etoxazole (0.026 μg/larvae); and 8s showed the best larvicidal activity against P. xylostella with an LC50 value of 0.27 mg/mL, which was 3.37-fold that of toosendanin and slightly higher than that of etoxazole (0.28 mg/mL). Furthermore, the control efficacy of 8s against P. xylostella in the pot experiments under greenhouse conditions was better than that of etoxazole. Structure–activity relationships (SARs) revealed that in most cases, the introduction of 1,3,4-oxadiazole/thiadiazole containing halophenyl groups at the C-13 position of (+)-nootkatone could obtain more active derivatives against M. separata, M. persicae, and P. xylostella than those containing other groups. In addition, toxicity assays indicated that these (+)-nootkatone derivatives had good selectivity to insects over nontarget organisms (normal mammalian NRK-52E cells and C. idella and N. denticulata fries) with relatively low toxicity. Therefore, the above results indicate that these (+)-nootkatone derivatives could be further explored as new lead compounds for the development of potential eco-friendly pesticides.
The purpose of this study was to investigate the neuroprotective effect of Arg-containing peptides from walnut storage protein sequences in scopolamine-induced zebrafish and further to validate the ...potential neuroprotection of Arg-containing peptide enriched walnut hydrolysates prepared by in silico hydrolysis and controlled enzymatic release. Results showed that walnut derived Arg-containing peptides with high abundance and great bioactivity predicted by bioinformatics displayed potent neuroprotection in scopolamine-induced zebrafish, and regulation of neurotransmitter level and antioxidant enzyme activity might be the main target for Arg-containing peptides to exert neuroprotection. Notably, Arg-containing peptides (not free arginine) contributed greater neuroprotection, and the positive charge and cell-penetrating properties also affected their neuroprotection. Subsequently, Arg-containing peptides could be released efficiently from walnut protein following hydrolysis by trypsin, pepsin, papain, and thermolysin (bound arginine content: ranging from 110.43 ± 1.58 to 121.82 ± 1.02 mg/g). Among them, trypsin had excellent potential for releasing Arg-containing peptides in silico hydrolysis, and its hydrolysate was confirmed to have neuroprotective capacity, indicating that the combination of in silico hydrolysis and controlled enzymatic release might be an effective approach to obtain Arg-containing neuroprotective peptides.
The study aimed to explore umami peptides derived from protein hydrolysates of Morchella esculenta. According to the electronic tongue and sensory evaluation, the ultrafiltration fractions (<3 kDa) ...of the protein hydrolysates exhibited the strongest umami taste. The overall flavor of the screened fractions was significantly improved after the Maillard reaction, based on the electronic nose and electronic tongue analyses, and the content of total free amino acid increased from 387.35 to 589.30 μg/mL. A total of 37 peptides with high confidence were identified from the fractions using LC-MS/MS. Additionally, two novel umami peptides were screened through bioinformatics and molecular docking, and their recognition threshold was 0.43 (EYPPLGRFA) and 0.52 mmol/L (TVIDAPGHRDFI), respectively. In addition, molecular docking analysis revealed that the key binding sites, such as Ser148, Leu51, Arg327, and Leu468 in T1R1/T1R3 contributed to docking, and hydrogen bonding and hydrophobic interactions were the dominant interaction forces between the two umami peptides and T1R1/T1R3 receptor. This study contributes to the development and utilization of Morchella esculenta in flavored foods.
(+)-Nootkatone, first isolated from the heartwood of Alaska yellow cedar (Chamaecyparis nootkatensis), is a non-food natural sesquiterpene ketone. Due to its strong grapefruit aroma and wide range of ...biological activities, there is a growing demand for (+)-nootkatone in the food, cosmetic, pharmaceutical, and chemical industries. Therefore, there is a need to combine the latest and previously available information to understand the research status of (+)-nootkatone and to pave a way for the further development of (+)-nootkatone and its analogs. The present work reviews the research progress in the plant sources, chemical synthesis, biosynthesis, and structural modifications of (+)-nootkatone, and the pesticidal and other physiological activities of (+)-nootkatone and its derivatives. We hope this work can provide a reference for the further application of (+)-nootkatone and its analogs in the food, cosmetic, pharmaceutical, and chemical industries.
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•(+)-Nootkatone, a natural sesquiterpene ketone, can be isolated from many plants.•Detailed discussion of the chemical and biosynthesis approaches of (+)-nootkatone.•Structural modifications of (+)-nootkatone were summarized.•(+)-Nootkatone and its analogs exhibited a wide range of biological activities.
The polysaccharide obtained from edible fungi has been regarded as the major bioactive component related to the nutritional and human's health. In the present study, three purified polysaccharides ...(LCP-1, LCP-2, and LCP-3) were obtained from Leccinum crocipodium (Letellier.) Watliag. The characterizations of LCP-1, LCP-2, and LCP-3 were determined by high-performance liquid chromatography (HPLC), UV, FT-IR spectrometrys and 1H NMR spectrum. LCP-1 had a molecular weight of 2.303 × 105 Da and 7.519 × 103 Da, and was composed of mannose (Man), ribose (Rib), rhamnose (Rha), glucuronic acid (GluA), galacturonic acid (GalA), glucose (Glu), galactose (Gal), xylose (Xyl), arabinose (Ara) and fucuronic (Fuc). The molecular weight of LCP-2 was 2.655 × 105 Da, and its monosaccharide constituents were Man, Rib, Rha, GluA, Glu, Gal, Xyl, Ara and Fuc. The molecular weight of LCP-3 was 3.783 × 105 Da, and its monosaccharide constituents were Man, Rib, Rha, GluA, GalA, Glu, Gal, Xyl, Ara and Fuc. For the in vitro immunomodulatory experiments demonstrated that three purified polysaccharides could enhance immunomodulatory activities on macrophage RAW 264.7 cells, moreover, LCP-2 and LCP-3 showed stronger immunomodulatory activity than LCP-1. The results indicated that the LCP-1, LCP-2, and LCP-3 could be further developed as functional food or medicine.
•Leccinum crocipodium (Letellier.) Watliag polysaccharides (LCP) were separated into three purified polysaccharides.•The monosaccharide composition, molecular weight and conformation of LCP-1, LCP-2, and LCP-3 were characterized.•LCP-1, LCP-2, and LCP-3 demonstrated immunomodulatory activity on macrophage RAW 264.7.
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•A series of novel honokiol thioethers bearing a 1,3,4-oxadiazole moiety were prepared.•Honokiol derivative 3k exhibited the best anti-proliferative activity against HCT116 cells.•3k ...can arrest HCT116 cells in G1 phase and induce HCT116 cell death.•3k directly inhibits the transcription and expression of YAP protein without activating the Hippo signaling pathway.
Honokiol, derived from Magnolia officinalis (a traditional Chinese medicine), has been reported to have anticancer activity. Here, a series of novel honokiol thioethers bearing a 1,3,4-oxadiazole moiety were prepared and evaluated for their anticancer activities against three types of digestive system tumor cells. Biological evaluation showed that honokiol derivative 3k exhibited the best antiproliferative activity against HCT116 cells with an IC50 value of 6.1 μmol/L, superior to the reference drug 5-fluorouracil (IC50: 9.63 ± 0.27 µmol/L). The structure–activity relationships (SARs) indicated that the introduction of –(4-NO2)Ph, 3-pyridyl, –(2-F)Ph, –(4-F)Ph, –(3-F)Ph, –(4-Cl)Ph, and –(3-Cl)Ph groups was favorable for enhancing the anticancer activity of the title honokiol thioethers. Further study revealed that honokiol thioether 3k can well inhibit the proliferation of colon cancer cells HCT116, arresting the cells in G1 phase and inducing cell death. Moreover, a preliminary mechanism study indicated that 3k directly inhibits the transcription and expression of YAP protein without activating the Hippo signaling pathway. Thus, honokiol thioether 3k could be deeply developed for the development of honokiol-based anticancer candidates.
Our previous study proved that the peptide MOp2 from Moringa oleifera seeds exhibited membrane-damaging effects on Staphylococcus aureus. In this study, TMT-based proteomics technology was mainly ...used to investigate the antimicrobial mechanism of MOp2 against S. aureus. A total of 541 differentially expressed proteins (DEPs) were identified in S. aureus treated with MOp2, among which 256 and 285 DEPs were upregulated and downregulated, respectively. They were mainly involved in inositol phosphate metabolism, S. aureus infection, citrate cycle (TCA cycle), and phosphotransferase system (PTS) and acted as ABC transporters and ribosomes. Moreover, the decreasing AKP activity indicated that MOp2 affected cell wall biosynthesis, and excessive ROS accumulation caused apoptosis, resulting in DNA fragmentation, nuclear morphological changes, and phosphatidylserine externalization. Additionally, molecular docking showed that MOp2 could interact with eight DEPs, including ProC, QoxB, SOD2, DnaK, GroEL, RplY, AcpS, and FabG, indicating that MOp2 might act on these molecular targets, leading to increased cell permeability, oxidative damage, impaired protein synthesis, cell wall synthesis obstruction, and energy metabolism disorder. Overall, these findings provided new insights into the multi-targeted mechanism of MOp2 against S. aureus, and could provide a theoretical basis for its application as a novel food preservative and antibiotic substitute.
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•Multi-targeted mechanism of MOp2 against Staphylococcus aureus was investigated.•A total of 541 differentially expressed proteins were identified in S. aureus treated with MOp2.•MOp2 could increase ROS accumulation, resulting in S. aureus apoptosis.•Molecular docking showed that MOp2 may act on eight protein targets in S. aureus.
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•A series of novel (+)-nootkatone derivatives were synthesized by 3 + 2 annulation.•Compounds 2i and 2 w showed significant growth inhibitory (GI) activity.•Derivative 2 r displayed ...more potent larvicidal activity than toosendanin.•The potent compounds 2 h, 2 l, 2p, 2 r and 2 w exhibited relative low toxicity to mammalian cells.•Some interesting results of structure-activity relationships were also observed.
(+)-Nootkatone, isolated from the heartwood of Alaska yellow cedar, Citrus Rutaceae and Alpinia Zingiberaceae, is a natural bicyclic sesquiterpene. Toward the discovery of new natural products-based insecticides, twenty-five novel (+)-nootkatone derivatives containing isoxazoline moiety were designed and prepared by 3 + 2 cycloaddition. Structures of all (+)-nootkatone derivatives were confirmed by different spectral analyses, in which compound 2 h was further identified by X-ray diffraction. Compounds 2 g, 2i, 2q, 2 u, 2 w and 2y displayed more effective insecticidal activities against both Mythimna separata Walker and Plutella xylostella Linnaeus than the botanical insecticide, toosendanin. Especially, derivatives 2i and 2 w showed significant growth inhibitory (GI) activity with the final mortality rates (FMRs) both of 73.3%. Derivative 2 r exhibited pronounced larvicidal activity with LC50 values of 0.23 μmol mL−1. In addition, the structure–activity relationships (SARs) of these (+)-nootkatone derivatives were also observed. Moreover, the potent compounds 2 h, 2 l, 2p, 2 r and 2 w exhibited relative low toxicity to mammalian cells (RAW 264.7).
