Search Results (3,905)

Avicennia marina, commonly known as the grey mangrove, is a salt-tolerant species widely distributed in coastal and estuarine ecosystems. Traditionally, it has been used in folk medicine to treat skin diseases, rheumatism, and ulcers due to its anti-inflammatory and antimicrobial properties. However, comprehensive studies on the chemical constituents and their pharmacological effects remain limited. The dried powder of the aerial parts of A. marina (3.6 kg) was successfully extracted three times with methanol (20 L × 3, each for 2 h) using a multifunctional ultrasonic cleaner operated at 25 °C with a 50% amplitude setting. In this study, the methanolic extract of the aerial parts of A. marina led to the isolation of eight compounds, including two previously unreported iridoid glycosides—avicenosides A and B (1 and 2)—and six known compounds: techtochrysin (3), 7,4′-di-O-methyl-apigenin (4), luteolin (5), kaempferol (6), trans-caffeic acid (7), and 3,4-dihydroxybenzoic acid (8). Their chemical structures were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and compared with previously published data. Moreover, the absolute configuration of the sugar moieties in the new compounds was also identified. All isolated compounds were evaluated for their cytotoxicity against HepG2 and A549 cancer cell lines. The results indicate potential cytotoxicity of the secondary metabolites from A. marina and provide evidence of their promising role as lead compounds for the development of novel anticancer agents. Full article

Siraitia grosvenorii (S. grosvenorii), a traditional medicine food homology plant, serves both dietary and medicinal purposes and is increasingly exploited for its bioactivities in pharmaceuticals and nutritional value. In this research, fifteen glycosides including three new cucurbitane-type triterpenoid glycosides named Luohanguosides A–C (1–3) and twelve known ones (4–15) have been isolated from the aqueous extract of fresh S. grosvenorii fruits. A comprehensive analysis of 1D, 2D-NMR, HRESIMS techniques along with some other spectroscopic methods led to the elucidation of their chemical structures. Further investigation focused on the hepatoprotective activities of compounds 1–15. It turned out that compounds 1, 5, and 10 exhibited significant hepatoprotective activities compared to bicyclol under the same concentration (20 μM), providing scientific support for further research on S.grosvenorii products for their preventive potential of hepatic diseases. Full article

Drug repurposing refers to the systematic identification of new therapeutic uses for existing drugs. Unlike traditional de novo drug discovery, which is expensive and time-consuming, repurposing leverages compounds with already established safety, pharmacokinetic, and pharmacodynamic profiles. In this study, we propose a drug repositioning model based on low-dimensional transcriptomic representations to investigate the relationship between known anticancer drugs and non-anticancer compounds. We analyzed LINCS L1000 data (1170 drugs; 824 anticancer, 346 non-anticancer). Data were projected with UMAP, PCA, and t-SNE. For each anticancer drug and for each method, we retrieved the k = 5 nearest non-anticancer neighbors and ranked candidates by recurrence frequency across all anticancer queries. We identified Ergometrine, Mupirocin, and (S)-blebbistatin among the most frequent non-anticancer drugs with a close association with drugs known to be anticancer. In addition, we performed a local neighborhood enrichment around the three candidates. Regarding Ergometrine (DB01253), in UMAP, 44/50 neighbors were anticancer (88.0% vs. global baseline 70.5%; hypergeometric BH-adjusted p = 0.0039). Considering (S)-blebbistatin (DB01944) in UMAP, 41/50 neighbors were anticancer (82.0% vs. 70.5%; BH-adjusted p = 0.0435). Mupirocin (DB00410) in UMAP had 44/50 neighbors as anticancer (88.0% vs. 70.5%; BH-adjusted p = 0.0039). Future research should explore the three drugs with in vivo models, investigating their possible synergies. Full article

Ilicic acid, nerolidol, and 9-hydroxynerolidol are major components of the aerial parts of Dittrichia viscosa. These components were selectively isolated in multigram quantities and used as lead compounds to generate diversity in the search for new natural-product-derived pesticides. A total of 29 derivatives of these three molecules—some of which are known natural products—were generated by subjecting these natural products to different transformations. In order to explore potential applications in sustainable biocontrol, some of the compounds generated were evaluated for plant protection potential against insect pests (Spodoptera littoralis, Myzus persicae, Rhopalosiphum padi), against the nematode Meloidogyne javanica, and for their phytotoxic effects on ryegrass (Lolium perenne) and lettuce (Lactuca sativa). Additionally, their effects against the tick Hyalomma lusitanicum have been tested. Compound 11 was found to be antifeedant against S. littoralis and nematicidal. Compounds 3a and 8 were potent antifeedants against R. padi. None of the tested compounds significantly inhibited lettuce growth, and compounds 17, 3, and 3a even promoted root development. Conversely, compounds 3, 4, 11, 17, and 21a exhibited strong herbicidal activity on ryegrass. In larvicidal assays against H. lusitanicum, compounds 3, 3a, 11, 17, 29, and 33 were active, with compound 29 being six times more active than the positive control nootkatone. Full article

Aronia melanocarpa is rich in anthocyanins, compounds with significant medicinal and industrial value, making it an attractive species for enhanced production. Compared with fruits or intact plants, callus tissue offers a uniform, controllable in vitro system that is particularly suitable for dissecting regulatory mechanisms under defined environmental conditions. Although light quality is known to influence anthocyanin biosynthesis, its specific regulatory mechanisms in A. melanocarpa remain unclear. In this study, callus tissues were cultured under six light regimes: full-spectrum LED, blue:red (5:1), red:blue (5:1), red:blue:white (1:1:1), red:white (5:1), and pure blue light. Anthocyanin content was quantified using the pH differential method, and the results showed that the blue:red (5:1) treatment produced the highest accumulation, reaching 14.06 mg/100 g. Transcriptome sequencing was then performed to compare the gene expression profiles between calli cultured under blue:red (5:1) light and those maintained in darkness. A total of 10,547 differentially expressed genes (DEGs) were identified, including 6134 upregulated and 4413 downregulated genes. Functional enrichment analysis indicated that these DEGs were mainly involved in anthocyanin biosynthesis and transport. Importantly, key structural genes such as PAL, C4H, 4CL, CHS, ANS, UFGT, and GST were significantly upregulated under blue:red (5:1) light, as further validated by qRT-PCR. Overall, our findings demonstrate that a blue:red (5:1) light ratio enhances anthocyanin accumulation by promoting the expression of biosynthetic and transport-related genes. This study not only provides new transcriptomic insights into the light-mediated regulation of secondary metabolism in A. melanocarpa callus, but also establishes a foundation for optimizing in vitro culture systems for sustainable anthocyanin production. Full article

Background/Objectives: Colorectal carcinoma (CRC) is among the most commonly diagnosed cancers in both men and women. Although CRC mortality is generally decreasing, new therapeutic options are needed for unresponsive subgroups of CRC patients. Methods: A series of known and new tyrphostin derivatives was tested for their efficacy against three CRC cell lines with varying KRAS, p53, and/or BRAF statuses. Growth inhibition, apoptosis induction, and inhibition of EGFR and VEGFR-2 were investigated. Results: Tyrphostin A9, the known RG13022-related tyrphostin 1a and its dichlorido(p-cymene)ruthenium(II) complex 1b, and the new SF₅-substituted compounds 2a and 2b showed selective antiproliferative activity against KRAS-mutant HCT-116 CRC cells expressing wildtype p53, while p53-knockout HCT-116 and KRAS-wildtype BRAF/p53-mutant HT-29 CRC cells were distinctly less sensitive. In HCT-116 cells, only tyrphostin A9 increased mRNA expression of caspases 3 and 8, as well as the kinases MEK1 and MEK2, whereas 2a reduced caspase 8 mRNA levels. Tyrphostin A9 increased caspase 3 activity and induced apoptosis in HCT-116 p53-wildtype cells while simultaneously inhibiting the receptor tyrosine kinases EGFR and VEGFR-2 at low nanomolar concentrations. Conclusions: Tyrphostin A9 could be a promising therapeutic option for the treatment of KRAS-mutant CRC that expresses wildtype p53. Full article

Non-alcoholic beer is increasingly popular worldwide but still faces flavor challenges compared to regular beer. These flavor-related challenges include pronounced ‘wort-like’ notes, excessive sweetness, and a lack of desirable aroma complexity. The industry is trying to improve the taste of non-alcoholic beer by trying new techniques and yeasts. A newly isolated maltose-negative brewer’s yeast (M-I) from an industrial-scale brewery collection has attracted attention due to its reduced wort-like flavor. This study aims to characterize the volatile profile of a newly isolated maltose-negative brewer’s yeast (M-I) in comparison with the well-known Saccharomycodes ludwigii. The novelty of this work lies in evaluating the aroma potential of a maltose-negative isolate newly applied in industrial brewing and its contribution to improving the flavor quality of non-alcoholic beer. An SPME-GC/MS system was used to analyze aroma compounds. According to volatile compound analysis, the M-I sample has higher amounts of esters and higher alcohol composition than the S. ludwigii beer sample. Also, it has lower amounts of Strecker aldehydes, which can give a worty off-flavor. Sensory analysis revealed that, interestingly, the control S. ludwigii sample was rated as having stronger ester notes, along with more pronounced sour and bitter characteristics, whereas the M-I sample was perceived as having a more balanced flavor, leading to a more favorable rating by the panelists. Full article

Four new compounds and three new natural products (1−7), including three novel cyclic tetrapeptides (penicopeptides B−D), along with three known spiroquinazoline analogs (8–10), were isolated from rice medium cultures of a sponge-associated Penicillium sp. SCSIO41035. The structural elucidations, including the determination of absolute configurations, were accomplished by comprehensive analyses utilizing NMR spectroscopy, HRESIMS, optical rotation data, X-ray crystallography experiments and electronic circular dichroism calculations. Differential NMR signals between symmetric units in cyclotetrapeptides 1 and 2 arise from the asymmetric solution conformations as investigated through conformational searching and theoretical calculations. The asymmetric conformations were primarily caused by the flexibility of the tyrosine residue’s phenyl side chain, with its substantial electron density significantly influencing the NMR signals of nearby groups. Bioactivity screening results displayed that isolated compounds demonstrated good neuraminidase inhibitory activity, with inhibition rates ranging from 43.16% to 85.40% at a concentration of 100 µg/mL. Full article

Background/Objectives: Hypericum cerastoides (Spach) N. Robson is a lesser-known species with potential pharmacological importance. This study aimed to profile phenolic compounds in its aerial parts and assess biological activities of isolated constituents, focusing on radical-scavenging, anti-α-glucosidase, and pro-lipase effects. Methods: Phenolic compounds from H. cerastoides aerial parts were dereplicated via UHPLC-HRMS/MS. The structures of isolated compounds were determined using spectroscopic methods (1D and 2D NMR, UV, and HRMS-ESI). Radical-scavenging was evaluated by DPPH and ABTS assays; anti-α-glucosidase and pro-lipase activities were measured by LC-MS. Results: UHPLC-HRMS profiling of a hydroalcoholic extract tentatively identified and quantified 39 phenolic compounds, mainly flavonoids and hydroxycinnamic acid derivatives. Furthermore, two new phenolic compounds, namely hypercerastoside A (HC4) and hypercerastoside B (HC6), together with three known compounds, coumaroylquinic acid (HC1), myricetin-3-O-glycoside (HC2), and myricetin-3-O-galactoside (HC3), as well as two artifacts, namely methyl ester of chlorogenic acid (HC5) and hypercerastoside C (HC7), were isolated from the ethylacetate extract of the aerial parts of title plant. Compounds HC2, HC3, and HC5 displayed the highest radical-scavenging activity. The anti-α-glucosidase test showed that compounds HC1 (IC₅₀ = 44 µM) and HC3 (IC₅₀ = 206 µM) possessed similar activity to acarbose (IC₅₀ = 206 µM). Myricetin glycosides HC2 and HC3 enhanced lipase activity fivefold at 200 µM. Conclusions: H. cerastoides is a promising source of bioactive phenolic compounds with significant radical-scavenging and enzyme-modulating activities. These preliminary findings support further exploration of its therapeutic potential, especially for oxidative stress-related disorders, type 2 diabetes, and cachexia. Full article

The extensive use of submicron emulsion systems, particularly those stabilized by nonionic surfactants, with their proven effectiveness and safety profile, provides a reassuring foundation for our research. Consequently, we designed and engineered new submicron emulsion formulations stabilized with a biocompatible surfactant polyoxyethylated cocoamine, whose nonionic character is due to a high degree of polyoxyethylation. We chose oleic acid as the oil phase, a fatty acid known for its beneficial properties. This led to novel biocompatible nanoemulsions with high stability and cosurfactant-free microemulsions. The dynamic light scattering studies confirmed that both formulations have a nanometric size and low polydispersity index values. Moreover, transmission electron microscopy verified the nanodroplets’ morphological homogeneity and spherical shape. The resulting nanoplatforms can be applied to carry bioactive agents in the pharmaceutical and cosmetic fields. For this reason, we solubilized newly synthesized 5-dimethylamino-5′-nitro-2,2′-bithiophene as a model hydrophobic cargo for delivering poorly water-soluble compounds. This dye was chosen due to its strong solvatochromic behavior and suitability for micropolarity analysis via UV–Vis spectroscopy. We also present a simple method for rapid micropolarity screening to assess the type of nanodispersion via solvatochromic shift as an alternative procedure for evaluating of the oils used to fabricate nanoformulations for pharmaceutical and cosmetic purposes. Full article

Neuroendocrine neoplasms (NENs) represent a small and heterogeneous group of tumors that share a common phenotype, originating from cells within the endocrine and nervous systems. Metallodrugs have had a significant impact on the treatment of NENs, as platinum-based chemotherapy is the first-line therapy approved for managing these types of tumors. Currently, medicinal inorganic chemistry is investigating new metal-based drugs to mitigate the side effects of existing agents, including cisplatin and its derivative compounds. Among the emerging alternatives to platinum-based drugs, ruthenium-based complexes garnered attention as potential chemotherapeutics due to their notable antineoplastic and antimetastatic activity. This review focuses on the promising antitumor effects of certain Ru compounds in NEN therapy, emphasizing their potential in NEN treatment through interaction with new potential targets. Among these, IT-139 (also known as KP-1339 or NKP-1339), which has already entered clinical trials, and other new Ru compounds are highlighted. Full article

Sulfonamides represent a versatile class of biologically active compounds, best known for their antibacterial activity, but increasingly investigated for their potential in oncology. Free sulfonamides themselves display cytotoxic properties; however, coordination with metal ions often enhances both selectivity and potency, while also introducing new mechanisms of action. Although numerous studies have reported sulfonamide–metal complexes with anticancer activity, a systematic overview linking biological properties to the central metal atom has been lacking. This review summarizes current research on sulfonamide complexes with transition metals and selected main-group elements, focusing on their pharmacological potential as anticancer agents. The compounds discussed include complexes of titanium, chromium, manganese, rhenium, ruthenium, osmium, iridium, palladium, platinum, copper, silver, gold, iron, cobalt, nickel, uranium, calcium, magnesium and bismuth. For each group, representative structures are presented along with cytotoxicity data against cancer cell lines, comparisons with reference drugs such as for example cisplatin, and where relevant, studies on carbonic anhydrase inhibition. The survey of available data demonstrates that many sulfonamide–metal complexes show cytotoxic activity comparable to or greater than existing chemotherapeutic agents, while in some cases exhibiting reduced toxicity toward non-cancerous cells. These findings highlight the promise of sulfonamide–metal complexes as a fertile area for anticancer drug development and provide a framework for future design strategies. This review covers the research on anti-cancer activity of sulfonamide complexes during the years 2007–2025. Full article

Using the one-strain-many-compounds (OSMAC) culturing approach, metabolomic studies, and bioassay-guided purification, we have isolated and characterised three new chlorinated natural products, agelolines B-D (1–3), together with two known compounds, ageloline A (4) and gausemycin A (5), which have been identified by high-resolution mass spectrometry and 1D and 2D NMR analyses. The preliminary evaluation of three small-scale extracts (M400, R358 and SGG) against the fish pathogen, Aeromonas salmonicida subsp. achromogenes KELDUR265-87, showed that the R358 extract displayed significant activity. Furthermore, the natural products (1–5) were evaluated against the fish pathogen Aeromonas salmonicida and human pathogens (Stenotrophomonas maltophilia L2125, Staphylococcus aureus ATCC6538P, and S. pneumoniae L44) using a serial dilution assay. Compound 3 displayed activity against Staphylococcus aureus ATCC6538P, S. maltophilia L2125, and S. pneumoniae L44 with MIC values of 6, 32, and 64 µg/mL, respectively. Interestingly, only gausemycin A (5) exhibited considerable inhibition against A. salmonicida with an MIC value of 32 µg/mL, and the activity increased by two-fold when supplemented with 0.45 mM calcium salt, while 2 and 4 showed moderate inhibition against S. maltophilia L2125. The biosynthetic pathways of compounds 1–4 were proposed. This is the first report of specific inhibition of A. salmonicida by 5. Full article

Type 2 Diabetes Mellitus (T2DM) is increasingly affecting individuals across various age groups due to inadequate insulin action and secretion. It has become the leading cause of mortality worldwide, with an estimated 9.3% of the global population currently affected. Recent epigenetic studies have shown that variations such as DNA methylation and histone modifications are implicated in the development of T2DM. However, epigenetically related conditions are known to be reversible, which could potentially pave the way for predicting and treating T2DM. This has led to the development of epigenetic modifier drugs, including histone deacetylase inhibitors (HDACi), histone acetyltransferase inhibitors (HATi), protein arginine methyltransferase inhibitors (PRMTi), DNA methyltransferase inhibitors (DNMTi), histone demethylating inhibitors (HDMi), and sirtuin-activating compounds (STAC). A major challenge with these epigenetic drugs is that only a few have been approved for treating metabolic diseases due to their potential to negatively impact off-target genes. The low specificity of these drugs can lead to side effects and increased toxicity, contributing to complex diseases such as cancer. Hence, gaining a comprehensive understanding of the epigenetic mechanisms underlying metabolic diseases can provide new insights and strategies for preventing, diagnosing, and treating metabolic disorders, such as T2DM. This review summarizes the epigenetic variations in T2DM, pharmaco-epigenetics, and the challenges surrounding epigenetics. This provides basic insight into the discovery of novel drug targets, which can lead to the development of epigenetic therapies for T2DM. Hence, the reversible nature of epigenetic variations retains hope for future novel strategies to combat T2DM. Full article

Network pharmacology, molecular docking, and molecular dynamics (MD) studies were used to investigate the molecular targets and mechanisms of action of Melissa officinalis phytoconstituents in type-2 diabetes mellitus (T2DM). SciFinder was used to retrieve previously known phytoconstituents from M. officinalis aerial parts. Targets related to these compounds were predicted using the Swiss TargetPrediction, SEA (similarity ensemble approach) and BindingDB databases, and were intersected with T2DM-relevant targets from public databases. Networks were constructed using the STRING online tool and Cytoscape (v.3.9.1) software. Gene ontology/KEGG pathway analysis was performed using DAVID and SHINEGO 0.77. Molecular docking used the MOE suite. MD simulations were conducted for 100 ns using GROMACS 2023 with a CHARMM36 force field. A total of 17 phytoconstituents and 154 targets associated with T2DM were identified. The protein–protein interaction (PPI) and target–pathway (TP) network analysis identified key hub genes, including EGFR, SRC, AKT1, TNF, PPARG, PIK3R1, RELA, INSR, GSK3B, PIK3CG, FYN, PTBIN, and PPARA, with critical roles in insulin resistance and T2DM-relevant pathways. The pathway enrichment analysis highlighted notable involvement in insulin signaling, inflammation, and diabetic complications. The compound–target (CT) network predicted quercetin, luteolin, ursolic acid, isoquercitrin, 2α-hydroxy-ursolic acid, and oleanolic acid to be key bioactive compounds. Molecular docking, followed by MD studies, identified that isoquercitrin showed most energetically favorable and stable complexes with three targets, namely EGFR, PPARα, and AKT1. These findings enhance our understanding of the antidiabetic potential of M. officinalis and underscore the need for further studies on its phytoconstituents, such as isoquercitrin, in search for new antidiabetic agents. Full article