Molecules最新文献

{"title":"Comparison of High-Efficiency MgO/Na₂CO₃ and MgO/K₂CO₃ as Heterogeneous Solid Base Catalysts for Biodiesel Production from Soybean Oil.","authors":"Xiangyang Li, Xunxiang Jia, Weiji Li, Shufan Jia, Siwei Zhang, Jiliang Song, Jiao Wang","doi":"10.3390/molecules30132876","DOIUrl":"10.3390/molecules30132876","url":null,"abstract":"<p><p>As a renewable alternative to fossil fuels, the industrial production of biodiesel urgently requires the development of efficient and recyclable solid base catalysts. In this study, the physicochemical properties and catalytic performance differences between MgO/Na₂CO₃ and MgO/K₂CO₃ catalysts were systematically compared using soybean oil as the raw material. By regulating the calcination temperature (500-700 °C), alcohol-to-oil ratio (3:1-24:1), and metal carbonate loading (10-50%), combined with N₂ adsorption-desorption, CO₂-TPD, XRD, SEM-EDS, and cycling experiments, the regulatory mechanisms of the ionic radius differences between sodium and potassium on the catalyst structure and performance were revealed. The results showed that MgO/Na₂CO₃-600 °C achieved a FAME yield of 97.5% under optimal conditions, which was 1.7% higher than MgO/K₂CO₃-600 °C (95.8%); this was attributed to its higher specific surface area (148.6 m²/g vs. 126.3 m²/g), homogeneous mesoporous structure, and strong basic site density. In addition, the cycle stability of MgO/K₂CO₃ was significantly lower, retaining only 65.2% of the yield after five cycles, while that of MgO/Na₂CO₃ was 88.2%. This stability difference stems from the disparity in their solubility in the reaction system. K₂CO₃ has a higher solubility in methanol (3.25 g/100 g at 60 °C compared to 1.15 g/100 g for Na₂CO₃), which is also reflected in the ion leaching rate (27.7% for K⁺ versus 18.9% for Na⁺). This study confirms that Na⁺ incorporation into the MgO lattice can optimize the distribution of active sites. Although K⁺ surface enrichment can enhance structural stability, the higher leaching rate leads to a rapid decline in catalyst activity, providing a theoretical basis for balancing catalyst activity and durability in sustainable biodiesel production.</p>","PeriodicalId":19041,"journal":{"name":"Molecules","volume":"30 13","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12251140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Novel Tetra-Substituted Pyrazole Derivatives Using Microwave Irradiation and Their Anti-Leukemic Activity Against Jurkat Cells.","authors":"Felipe P Machado, Maria Clara Campos, Juliana Echevarria-Lima, Diego P Sangi, Carlos Serpa, Otávio Augusto Chaves, Aurea Echevarria","doi":"10.3390/molecules30132880","DOIUrl":"10.3390/molecules30132880","url":null,"abstract":"<p><p>Three previously synthesized ketene dithioacetals were used as intermediates to obtain four nucleophiles to synthesize ten tetra-substituted pyrazoles (<b>11</b>-<b>20</b>). This was achieved through microwave irradiation in ethanol as the solvent, yielding superb results ranging from 68.4% to 90.1%, in agreement with some of the principles of green chemistry. The proposed structures were determined using various spectroscopic techniques, including infrared spectroscopy and hydrogen and carbon-13 nuclear magnetic resonance. Furthermore, the compounds underwent in-silico evaluations using CLC-Pred and AdmetSAR software to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. This was combined with molecular docking calculations for four main cancer-related targets for pyrazole core, to facilitate screening for subsequent biological assessments. Based on the data generated from these analyses, it was identified two pyrazoles (<b>11</b> and <b>18</b>) likely to exhibit anti-tumor activity, while also demonstrating low toxicity levels. Upon selection, these two pyrazoles were subjected to toxicity assessments using the <i>Artemia salina</i> method and evaluated for their effects on the viability of Jurkat cancer cells with a potency of 45.05 and 14.85 µM to <b>11</b> and <b>18</b>, respectively, and with a potency of above 100 µM for the non-carcinogenic cells HEK 293. Overall, the findings from these studies indicate pyrazole derivatives as potential anti-tumor candidates.</p>","PeriodicalId":19041,"journal":{"name":"Molecules","volume":"30 13","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12251036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclodextrin-Based Quercetin Powders for Potential Nose-to-Brain Transport: Formulation and In Vitro Assessment.","authors":"Elmina-Marina Saitani, Paraskevi Papakyriakopoulou, Theodora Bogri, Georgia Choleva, Kyriaki Kontopoulou, Spyridon Roboras, Maria Samiou, Antiopi Vardaxi, Stergios Pispas, Georgia Valsami, Natassa Pippa","doi":"10.3390/molecules30132878","DOIUrl":"10.3390/molecules30132878","url":null,"abstract":"<p><p>Quercetin (Que) is widely recognized for its antioxidant and neuroprotective properties; however, its clinical potential remains limited due to poor solubility and low oral bioavailability. Nasal powders have emerged as a promising strategy to overcome these limitations, taking advantage of nose-to-brain delivery, offering a direct, non-invasive route to the central nervous system while bypassing first-pass metabolism. This study aims to extend previous work by systematically investigating the impact of different preparation methods (spray drying vs. lyophilization) and the incorporation of hydroxypropyl methylcellulose (HPMC) and mannitol/lecithin microparticles (MLMPs) on the physicochemical characteristics, structural properties, and in vitro diffusion behavior of HPβCD-based nasal powder formulations of Que. Thermal behavior and stability were analyzed using TGA, while morphology and particle distribution were assessed via Scanning Electron Microscopy. In vitro diffusion studies using Franz cells and regenerated cellulose membranes were conducted under simulated nasal conditions. Among all tested formulations, the spray-dried HPβCD/Que powder (F4) showed the highest permeation (0.11 ± 0.01 mg/cm² at 120 min). The inclusion of HPMC improved thermal stability but reduced Que diffusion, likely due to increased viscosity and matrix formation. Blending with MLMPs enhanced powder flow and dose placement, although it modestly reduced diffusion efficiency. Overall, this study highlights the potential of HPβCD-based spray-dried powders for nasal Que delivery and demonstrates how HPMC and MLMPs can be strategically employed to tailor performance characteristics.</p>","PeriodicalId":19041,"journal":{"name":"Molecules","volume":"30 13","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12251352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urolithin A Attenuates Periodontitis in Mice via Dual Anti-Inflammatory and Osteoclastogenesis Inhibition: A Natural Metabolite-Based Therapeutic Strategy.","authors":"Yishu Xia, Danni Wu, Linyi Zhou, Xinyu Wu, Jianzhi Chen","doi":"10.3390/molecules30132881","DOIUrl":"10.3390/molecules30132881","url":null,"abstract":"<p><p>Periodontitis is an inflammatory disease that affects the periodontal supporting tissues. Its cardinal clinical manifestations encompass gingival inflammation, periodontal pocket formation, and alveolar bone resorption. Urolithin A (UA), a gut microbiota-derived metabolite of ellagitannins, is known for its anti-inflammatory and osseous-protective properties. Nonetheless, the impact of UA on periodontitis remains unknown. To investigate the preventive effect of UA, we employed a lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 mouse macrophages, a receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation model, and a ligature-induced periodontitis model in mice. The expression of inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6) was analyzed to assess anti-inflammatory efficacy. Bone loss in mice with periodontitis was assessed through histological and imaging techniques, including haematoxylin and eosin staining to evaluate alveolar bone morphology, Masson's trichrome staining to visualize collagen fiber distribution, and micro-computed tomography scanning to quantify bone structural parameters. Additionally, we investigated the underlying mechanisms by examining osteoclast activity through tartrate-resistant acid phosphatase staining and the expression levels of proteins RANKL and osteoprotegerin (OPG). We found that UA reduced IL-6 and TNF-α levels in vitro and in vivo, inhibited osteoclast differentiation, and decreased the RANKL/OPG ratio in periodontitis mice.</p>","PeriodicalId":19041,"journal":{"name":"Molecules","volume":"30 13","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12251368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methyl Viologen@β-Zeolite with Absorption/Fluorescence Dual-Mode and Photo/Chemical Synergistic Stimuli-Responsive Chromism.","authors":"Jingxuan Han, Shaoning Li, Huihui Li, Yu Li, Jiaqiao Qin, Fuxiang Wang, Qinhe Pan","doi":"10.3390/molecules30132872","DOIUrl":"10.3390/molecules30132872","url":null,"abstract":"<p><p>In this work, methyl viologen (MV) was adsorbed into the nanopores of Si/Al H-β-zeolite via cation exchange. The resulting MV@β-zeolite possessed absorption/fluorescence dual-mode and photo/chemical synergistic stimuli-responsive chromism. Owing to the acidic surrounding provided by β-zeolite, the chromism of MV required the synergistic stimuli of UV irradiation and a chemical reductant (such as Na₂SO₃). UV irradiation induced single electron transfer from the chemical reductant to MV@β-zeolite, leading to enhanced absorption at 610 nm together with a daylight color change from pale yellow to blue. Meanwhile, the nanopores of β-zeolite inhibited aggregation-caused quenching of MV, enabling MV to emit cyan fluorescence at 500 nm. After the single electron transfer of the chemical reductant under UV irradiation, the cyan fluorescence of MV@β-zeolite was quenched. Additionally, MV@β-zeolite exhibited a short stimulus response time (250 s) and good color change reversibility. These findings in this work provide valuable insights into the design of multi-mode and synergistic stimuli-responsive viologen-based chromic materials, particularly for applications in secure high-throughput information storage, high-level anti-counterfeiting and multi-target multi-mode sensing.</p>","PeriodicalId":19041,"journal":{"name":"Molecules","volume":"30 13","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12251173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Potential of a New Nickel(II):Phenanthroline Complex with L-isoleucine as an Antitumor Agent: Design, Crystal Structure, Spectroscopic Characterization, and Theoretical Insights.","authors":"Jayson C Dos Santos, João G de Oliveira Neto, Ana B N Moreira, Luzeli M da Silva, Alejandro P Ayala, Mateus R Lage, Rossano Lang, Francisco F de Sousa, Fernando Mendes, Adenilson O Dos Santos","doi":"10.3390/molecules30132873","DOIUrl":"10.3390/molecules30132873","url":null,"abstract":"<p><p>This study presents the synthesis, physicochemical characterization, and biological evaluation of a novel ternary nickel(II) complex with isoleucine and 1,10-phenanthroline ligands, [Ni(Phen)(Ile)₂]∙6H₂O, designed as a potential antitumor agent. Single-crystal X-ray diffraction revealed a monoclinic structure (C2-space group) with an octahedral Ni(II) coordination involving Phen and Ile ligands. A Hirshfeld surface analysis highlighted intermolecular interactions stabilizing the crystal lattice, with hydrogen bonds (H···H and O···H/H···O) dominating (99.1% of contacts). Density functional theory (DFT) calculations, including solvation effects (in water and methanol), demonstrated strong agreement with the experimental geometric parameters and revealed higher affinity to the water solvent. The electronic properties of the complex, such as HOMO-LUMO gaps (3.20-4.26 eV) and electrophilicity (4.54-5.88 eV), indicated a charge-transfer potential suitable for biological applications through interactions with biomolecules. Raman and infrared spectroscopic studies showed vibrational modes associated with Ni-N/O bonds and ligand-specific deformations, with solvation-induced shifts observed. A study using ultraviolet-visible-near-infrared absorption spectroscopy demonstrated that the complex remains stable in solution. In vitro cytotoxicity assays against MCF-7 (breast adenocarcinoma) and HCT-116 (colorectal carcinoma) cells showed dose-dependent activity, achieving 47.6% and 65.3% viability reduction at 100 μM (48 h), respectively, with lower toxicity to non-tumor lung fibroblasts (GM07492A, 39.8%). Supporting the experimental data, we performed computational modeling to examine the pharmacokinetic profile, with particular focus on the absorption, distribution, metabolism, and excretion properties and drug-likeness potential.</p>","PeriodicalId":19041,"journal":{"name":"Molecules","volume":"30 13","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12251309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Graph Convolution and Attention Mechanism for Kinase Inhibition Prediction.","authors":"Hamza Zahid, Kil To Chong, Hilal Tayara","doi":"10.3390/molecules30132871","DOIUrl":"10.3390/molecules30132871","url":null,"abstract":"<p><p>Kinase is an enzyme responsible for cell signaling and other complex processes. Mutations or changes in kinase can cause cancer and other diseases in humans, including leukemia, neuroblastomas, glioblastomas, and more. Considering these concerns, inhibiting overexpressed or dysregulated kinases through small drug molecules is very important. In the past, many machine learning and deep learning approaches have been used to inhibit unregulated kinase enzymes. In this work, we employ a Graph Neural Network (GNN) to predict the inhibition activities of kinases. A separate Graph Convolution Network (GCN) and combined Graph Convolution and Graph Attention Network (GCN_GAT) are developed and trained on two large datasets (Kinase Datasets 1 and 2) consisting of small drug molecules against the targeted kinase using 10-fold cross-validation. Furthermore, a wide range of molecules are used as independent datasets on which the performance of the models is evaluated. On both independent kinase datasets, our model combining GCN and GAT provides the best evaluation and outperforms previous models in terms of accuracy, Matthews Correlation Coefficient (MCC), sensitivity, specificity, and precision. On the independent Kinase Dataset 1, the values of accuracy, MCC, sensitivity, specificity, and precision are 0.96, 0.89, 0.90, 0.98, and 0.91, respectively. Similarly, the performance of our model combining GCN and GAT on the independent Kinase Dataset 2 is 0.97, 0.90, 0.91, 0.99, and 0.92 in terms of accuracy, MCC, sensitivity, specificity, and precision, respectively.</p>","PeriodicalId":19041,"journal":{"name":"Molecules","volume":"30 13","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12251378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electronic Structure of the Ground and Low-Lying States of MoLi.","authors":"Constantinos Demetriou, Demeter Tzeli","doi":"10.3390/molecules30132874","DOIUrl":"10.3390/molecules30132874","url":null,"abstract":"<p><p>Molybdenum lithium compounds and materials are being researched and applied in cutting-edge industries; however, their bonding has not been explored in a systematic way. The present study investigates the MoLi molecule, to shed light on its bonding. Specifically, the electronic structure and bonding of the ground and 40 low-lying states of the MoLi molecule are explored, employing multireference methodologies, i.e., CASSCF and MRCISD(+Q) in conjunction with the aug-cc-pV5z(-PP) basis set. Bond distances, dissociation energies, dipole moments as well as common spectroscopic constants are given, while the potential energy curves are plotted. For the ground state, XΣ+6, it is found that Re = 2.708 Å, De = 24.1 kcal/mol, ωe = 316.8 cm-1, ωexe = 2.11 cm-1, and <i>μ</i> = 3.63 D. Overall, the calculated states present a variety of bonds, from weak van der Waals up to the formation of 2.5 bonds. The dissociation energies of the calculated states range from 2.3 kcal/mol (aΣ+8) to 34.7 (cΠ4), while the bond distances range from 2.513 Å to 3.354 Å. Finally, dipole moment values up to 3.72 D are calculated. In most states, a 2s2pz hybridization on Li and a 4dz25s5pz or 5s5pz hybridization on Mo are found. Moreover, it is observed that the excited Li(P2) atom forms the shortest bonds because its empty 2s0 orbital can easily accept electrons, resulting in a strong σ dative bond. Finally, the present work highlights the exceptional ability of lithium atoms to participate in a variety of bonding schemes, and it could provide the opening gate for further investigation of this species or associated material and complexes.</p>","PeriodicalId":19041,"journal":{"name":"Molecules","volume":"30 13","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12250845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Low-Eutectic Solvent Co-Culture-Assisted Whole-Cell Catalyzed Synthesis of Ethyl (<i>R</i>)-4-Chloro-3-Hydroxybutyrate.","authors":"Yanni Wang, Bo Liu, Yanmei Dai, Zijuan Tao, Lan Tang, Zhimin Ou","doi":"10.3390/molecules30132869","DOIUrl":"10.3390/molecules30132869","url":null,"abstract":"<p><p>In this study, CGMCC NO:28566, a strain that can efficiently convert Ethyl 4-chloroacetoacetate(COBE) to (<i>R</i>)-4-chloro-3-hydroxybutyrate((<i>R</i>)-CHBE), was screened by soil-sieving bacteria. In order to improve the transformation effect of the strain, the natural low-eutectic solvent (NADES), which can alter the cell permeability, was utilized for assisted catalysis, and a better catalytic effect was achieved. This study was carried out using a co-culture of strains with NADES and secondary addition of NADES on the basis of co-culture, and 10 NADESs were screened at the same time. The co-catalytic effect of 0.5% (<i>w</i>/<i>v</i>) choline chloride: urea (1:2) (ChCl:U (1:2)) was found to be the most significant, with a yield of (<i>R</i>)-CHBE reaching 89.1%, which was 58.2% higher than that of the control group, with a 99% ee value. Furthermore, the catalytic results demonstrated that the co-culture of the strain with NADES during fermentation yielded superior outcomes to the secondary addition of NADES during the reaction buffer. Furthermore, the catalytic effect of ChCl:U (1:2) was demonstrated to be superior to that of its individual components or single-component blends, due to its distinctive valence bonding advantage. The results indicate that the addition of 0.5% (<i>w</i>/<i>v</i>) ChCl:U (1:2) during the co-culture process has the effect of improving cell permeability to a certain extent, thereby increasing the contact between the substrate and the enzyme during the whole-cell catalytic reactions.</p>","PeriodicalId":19041,"journal":{"name":"Molecules","volume":"30 13","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12250896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies Used for the Discovery of New Microbial Metabolites with Antibiotic Activity.","authors":"Pablo Dasí-Delgado, Cecilia Andreu, Marcel Lí Del Olmo","doi":"10.3390/molecules30132868","DOIUrl":"10.3390/molecules30132868","url":null,"abstract":"<p><p>The discovery of new microbial metabolites is essential to combat the alarming rise in antimicrobial resistance and to meet emerging medical needs. This work critically reviews current strategies for identifying antimicrobial compounds, emphasizing the potential of microorganisms as a rich source of bioactive secondary metabolites. This review explores innovative methods, such as investigating extreme environments where adverse conditions favor the emergence of unique metabolites; developing techniques, like the iChip, to cultivate previously uncultivable bacteria; using metagenomics to analyze complex samples that are difficult to isolate; and integrates artificial intelligence to accelerate genomic mining, structural prediction, and drug discovery optimization processes. The importance of overcoming current challenges, such as replicating findings, low research investment, and the lack of adapted collection technologies, is also emphasized. Additionally, this work analyzes the crucial role of bacterial resistance and the necessity of a holistic approach involving new technologies, sustained investment, and interdisciplinary collaboration. This work emphasizes not only the current state of metabolite discovery but also the challenges that must be addressed to ensure a continuous flow of new therapeutic molecules in the coming decades.</p>","PeriodicalId":19041,"journal":{"name":"Molecules","volume":"30 13","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12251386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}