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Fitoterapia Jun 2024Bioactive compounds derived from natural sources have long been investigated for the prevention and treatment of human diseases. Sophoraflavanone G (SFG), a lavandulyl... (Review)
Review
Bioactive compounds derived from natural sources have long been investigated for the prevention and treatment of human diseases. Sophoraflavanone G (SFG), a lavandulyl flavanone naturally occurring in several Sophora plant species, belongs to the group of prenylated flavonoids that have garnered significant interest in contemporary research. The natural molecule exhibits a wide range of pharmacological properties and shows remarkable efficacy. Its ability to effectively suppress a range of malignant tumor cells, such as leukemia, breast cancer, and lung cancer, is attributed to its multi-target, multi-pathway, and multi-faceted mechanisms of action. Simultaneously, it can also alleviate various inflammatory diseases by mediating inflammatory mediators and molecular pathways. Furthermore, it has the capability to combat antibiotic resistance, exhibit synergistic antibacterial properties with diverse antibiotics, and prevent and treat various agricultural pests. Theoretically, it can bring benefits to human health and has potential value as a drug. Nevertheless, the drawbacks of poor water solubility and inadequate targeting cannot be overlooked. To comprehensively assess the current research on SFG, leverage its structural advantages and pharmacological activity, overcome its low bioavailability limitations, expedite its progression into a novel therapeutic drug, and better serve the clinic, this article presents a overall retrospect of the current research status of SFG. The discussion includes an analysis of the structural characteristics, physicochemical properties, bioavailability, pharmacological activities, and structure-activity relationships of SFG, with the goal of offering valuable insights and guidance for future research endeavors in this field.
PubMed: 38901805
DOI: 10.1016/j.fitote.2024.106080 -
Molecules (Basel, Switzerland) May 2024Isoflavones are a class of natural products that exhibit a wide range of interesting biological properties, including antioxidant, hepatoprotective, antimicrobial, and...
Isoflavones are a class of natural products that exhibit a wide range of interesting biological properties, including antioxidant, hepatoprotective, antimicrobial, and anti-inflammatory activities. Scandenone (), osajin (), and 6,8-diprenylgenistein () are natural prenylated isoflavones that share the same polyphenol framework. In this research, the key intermediate was used for the synthesis of the natural isoflavones -, establishing a stereoselective synthetic method for both linear and angular pyran isoflavones. The antibacterial activities of - were also evaluated, and all of them displayed good antibacterial activity against Gram-positive bacteria. Among them, was the most potent one against MRSA, with a MIC value of 2 μg/mL, and the SEM assay indicated that the bacterial cell membranes of both MRSA and could be disrupted by . These findings suggest that this type of isoflavone could serve as a lead for the development of novel antibacterial agents for the treatment of Gram-positive bacterial infections.
Topics: Anti-Bacterial Agents; Isoflavones; Microbial Sensitivity Tests; Molecular Structure; Methicillin-Resistant Staphylococcus aureus; Gram-Positive Bacteria; Biological Products; Enterococcus faecalis
PubMed: 38893450
DOI: 10.3390/molecules29112574 -
International Journal of Molecular... May 20244-O-Methyl-ascochlorin (MAC), a derivative of the prenyl-phenol antibiotic ascochlorin extracted from the fungus , shows anticarcinogenic effects on various cancer...
4-O-Methyl-ascochlorin (MAC), a derivative of the prenyl-phenol antibiotic ascochlorin extracted from the fungus , shows anticarcinogenic effects on various cancer cells. 5-Fluorouracil (5-FU) is used to treat colorectal cancer (CRC); however, its efficacy must be enhanced. In this study, we investigated the molecular mechanisms by which MAC acts synergistically with 5-FU to inhibit cell proliferation and induce apoptosis in CRC cells. MAC enhanced the cytotoxic effects of 5-FU by suppressing the Akt/mTOR/p70S6K and Wnt/β-catenin signaling pathways. It also reduced the viability of 5-FU-resistant (5-FU-R) cells. Furthermore, expression of anti-apoptosis-related proteins and cancer stem-like cell (CSC) markers by 5-FU-R cells decreased in response to MAC. Similar to MAC, the knockdown of CTNNB1 induced apoptosis and reduced expression of mRNA encoding CRC markers in 5-FU-R cells. In summary, these results suggest that MAC and other β-catenin modulators may be useful in overcoming the 5-FU resistance of CRC cells.
Topics: Humans; Fluorouracil; Colorectal Neoplasms; Wnt Signaling Pathway; Apoptosis; Drug Synergism; beta Catenin; Cell Proliferation; Cell Line, Tumor; Drug Resistance, Neoplasm; TOR Serine-Threonine Kinases
PubMed: 38891932
DOI: 10.3390/ijms25115746 -
Journal of Asian Natural Products... Jun 2024Three new prenylated C-C compounds (), together with two known prenylated C-C compounds () and one known C-C derivative (), were isolated from the roots of A. C. Smith....
Three new prenylated C-C compounds (), together with two known prenylated C-C compounds () and one known C-C derivative (), were isolated from the roots of A. C. Smith. The structures of were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, CD experiments and ECD calculations. The structure of illibrefunone A () was confirmed by single-crystal X-ray diffraction analysis. All compounds were evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated murine RAW264.7 macrophages and murine BV2 microglial cells, antiviral activity against Coxsackievirus B3 (CVB3) and influenza virus A/Hanfang/359/95 (H3N2). Compounds and exhibited potent inhibitory effects on the production of NO in RAW 264.7 cells with IC values of 20.57 and 12.87 μM respectively, which were greater than those of dexamethasone (positive control). Compounds and exhibited weak activity against Coxsackievirus B3, with IC values ranging from 25.87 to 33.33 μM.
PubMed: 38885306
DOI: 10.1080/10286020.2024.2365437 -
Frontiers in Chemistry 2024As inhibitors of advanced glycation end products (AGEs), such as pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with...
As inhibitors of advanced glycation end products (AGEs), such as pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with streptozotocin-induced diabetes, treatment with AGE inhibitors is believed to be a potential strategy for the prevention of aging, age-related diseases, and lifestyle-related diseases, including diabetic complications. In the present study, the MeOH extract of (EH; aerial parts of spp.) was found to inhibit the formation of -(carboxymethyl)lysine (CML) and -(carboxymethyl) arginine (CMA) during the incubation of collagen-derived gelatin with ribose. EH was purchased from Uchida Wakan-yaku Co., and a MeOH extract was prepared. Several steps of column chromatography purified the extract. Each fraction was tested for inhibitory activity by ELISA using monoclonal antibodies for CML and CMA. After activity-guided fractionation and purification by column chromatography, three new prenylflavonoids [named Koreanoside L (), Koreanoside E1 (), and Koreanoside E2 ()] and 40 known compounds (-) were isolated from EH, and their inhibitory effects against CML and CMA formation were tested. Among these, epimedokoreanin B (), epimedonin E (), epicornunin B (), and epicornunin F () inhibited the formation of both CML and CMA, with epimedokoreanin B () having the most potent inhibitory effect among the isolated compounds. To obtain the structure-activity relationships of , the phenolic hydroxy groups of were methylated by trimethylsilyl-diazomethane to afford the partially and completely methylated compounds of . Prenyl derivatives of propolis (artepillin C, baccharin, and drupanin) were used in the assay. As only showed significant activity among these compounds, the catechol group of the B ring and the two prenyl groups attached to the flavanone skeleton were essential for activity. These data suggest that could prevent the clinical complications of diabetes and age-related diseases by inhibiting AGEs.
PubMed: 38882216
DOI: 10.3389/fchem.2024.1407934 -
Frontiers in Microbiology 2024Fungi possess well-developed secondary metabolism pathways that are worthy of in-depth exploration. The One Strain Many Compounds (OSMAC) strategy is a useful method for...
Fungi possess well-developed secondary metabolism pathways that are worthy of in-depth exploration. The One Strain Many Compounds (OSMAC) strategy is a useful method for exploring chemically diverse secondary metabolites. In this study, continued chemical investigations of the marine red algae-derived endophytic fungus 2021CDF-3 cultured in PDB media yielded six structurally diverse indole derivatives, including two new prenylated indole alkaloids asperinamide B () and peniochroloid B (), as well as four related derivatives (compounds - and ). The chemical structures of these compounds, including the absolute configurations of and , were determined by extensive analyses of HRESIMS, 1D and 2D NMR spectroscopic data, and TDDFT-ECD calculations. Compound was found to possess an unusual 3-pyrrolidone dimethylbenzopyran fused to the bicyclo[2.2.2]diazaoctane moiety, which was rare in previously reported prenylated indole alkaloids. cytotoxic experiments against four human tumor cell lines (HeLa, HepG2, FADU, and A549) indicated that strongly inhibited the FADU cell line, with an IC value of 0.43 ± 0.03 μM. This study suggested that the new prenylated indole alkaloid is a potential lead compound for anti-FADU drugs.
PubMed: 38873167
DOI: 10.3389/fmicb.2024.1400803 -
Journal of Natural Products Jun 2024The unfolded protein response (UPR) is a key component of fungal virulence. The prenylated xanthone γ-mangostin isolated from (Clusiaceae) fruit pericarp, has recently...
The unfolded protein response (UPR) is a key component of fungal virulence. The prenylated xanthone γ-mangostin isolated from (Clusiaceae) fruit pericarp, has recently been described to inhibit this fungal adaptative pathway. Considering that (Calophyllaceae) is known for its high prenylated xanthone content, its stem bark extract was fractionated using a bioassay-guided procedure based on the cell-based anti-UPR assay. Four previously undescribed xanthone derivatives were isolated, caledonixanthones N-Q (, , , and ), among which compounds and showed promising anti-UPR activities with IC values of 11.7 ± 0.9 and 7.9 ± 0.3 μM, respectively.
Topics: Xanthones; Unfolded Protein Response; Calophyllum; Molecular Structure; Humans; Plant Bark
PubMed: 38869194
DOI: 10.1021/acs.jnatprod.4c00328 -
Ecotoxicology and Environmental Safety Jul 2024Marine biofouling remains a huge concern for maritime industries and for environmental health. Although the current biocide-based antifouling coatings can prevent marine...
Marine biofouling remains a huge concern for maritime industries and for environmental health. Although the current biocide-based antifouling coatings can prevent marine biofouling, their use has been associated with toxicity for the marine environment, being urgent to find sustainable alternatives. Previously, our research group has identified a prenylated chalcone (1) with promising antifouling activity against the settlement of larvae of the macrofouling species Mytilus galloprovincialis (EC = 16.48 µM and LC > 200 µM) and lower ecotoxicity when compared to Econea®, a commercial antifouling agent in use. Herein, a series of chalcone 1 analogues were designed and synthesized in order to obtain optimized antifouling compounds with improved potency while maintaining low ecotoxicity. Compounds 8, 15, 24, and 27 showed promising antifouling activity against the settlement of M. galloprovincialis larvae, being dihydrochalcone 27 the most potent. The effect of compound 24 was associated with the inhibition of acetylcholinesterase activity. Among the synthesized compounds, compound 24 also showed potent complementary activity against Navicula sp. (EC = 4.86 µM), similarly to the lead chalcone 1 (EC = 6.75 µM). Regarding the structure-activity relationship, the overall results demonstrate that the substitution of the chalcone of the lead compound 1 by a dihydrochalcone scaffold resulted in an optimized potency against the settlement of mussel larvae. Marine polyurethane (PU)-based coatings containing the best performed compound concerning anti-settlement activity (dihydrochalcone 27) were prepared, and mussel larvae adherence was reduced compared to control PU coatings.
Topics: Animals; Biofouling; Larva; Mytilus; Chalcones; Structure-Activity Relationship; Chalcone; Disinfectants
PubMed: 38865941
DOI: 10.1016/j.ecoenv.2024.116560 -
The American Journal of Chinese Medicine Jun 2024has been widely used in traditional Chinese medicine for over 1700 years. This plant is known for its heat-clearing, damp-drying, insecticidal, and diuretic properties....
has been widely used in traditional Chinese medicine for over 1700 years. This plant is known for its heat-clearing, damp-drying, insecticidal, and diuretic properties. Phytochemical research has identified prenylated flavonoids as a unique class of bioactive compounds in . Recent pharmacological studies reveal that the prenylated flavonoids from (PFS) exhibit potent antitumor, anti-inflammatory, and glycolipid metabolism-regulating activities, offering significant therapeutic benefits for various diseases. However, the pharmacokinetics and toxicological profiles of PFS have not been systematically studied. Despite the diverse biological effects of prenylated flavonoid compounds against similar diseases, their structure-activity relationship is not yet fully understood. This review aims to summarize the latest findings regarding the chemical composition, drug metabolism, pharmacological properties, toxicity, and structure-activity relationship of prenylated flavonoids from . It seeks to highlight their potential for clinical use and suggest directions for future related studies.
PubMed: 38864547
DOI: 10.1142/S0192415X24500447 -
Signal Transduction and Targeted Therapy Jun 2024Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific...
Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.
Topics: Humans; Respiratory Syncytial Virus Infections; Pyridines; Mice; Animals; Respiratory Syncytial Virus, Human; Viral Fusion Proteins; Farnesyltranstransferase; Antiviral Agents; Piperidines; Mice, Inbred BALB C; Protein Conformation; Dibenzocycloheptenes
PubMed: 38853183
DOI: 10.1038/s41392-024-01858-5