Pharmaceutical Science Advances最新文献

{"title":"Metabolomic profiling of Musanga cecropioides leaf extract reveals cytotoxic mechanisms in MCF-7 breast cancer cells","authors":"Olubusola O. Olaleye ,&nbsp;Dong-Hyun Kim ,&nbsp;Keith A. Spriggs","doi":"10.1016/j.pscia.2025.100107","DOIUrl":"10.1016/j.pscia.2025.100107","url":null,"abstract":"<div><div>Breast cancer is a leading cause of cancer-related mortality, necessitating novel therapeutic strategies. This study employed liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics to investigate the cytotoxic effects of <em>Musanga cecropioides</em> leaf extract (MCL) on MCF-7 breast cancer cell lines. Multivariate, univariate and pathway enrichment analyses were conducted to identify significantly altered metabolites and pathways. Rigorous metabolite identification was carried out using authentic standards, the human metabolome database (HMDB) and MS/MS mzCloud database. Following treatment, the orthogonal partial least squares-discriminant analysis (OPLS-DA) showed clear separation and clustering of sample groups with cross-validation values of R²Y = 0.998 and Q² = 0.992 in the OPLS-DA score plot. Furthermore, multivariate analyses revealed significant metabolic reprogramming, including alterations in glycerophospholipid metabolism, alanine, aspartate, and glutamate metabolism, and the TCA cycle. Ninety-seven (97) metabolites were significantly perturbed, with key changes observed in acetylcholine, phosphocholine, and citric acid levels. Pathway enrichment analysis identified disrupted metabolic pathways critical for cell growth and survival, highlighting potential therapeutic targets. These findings underscore the anticancer potential of MCL extract by modulating metabolic vulnerabilities in breast cancer cells and provide a foundation for further biomarker discovery and therapeutic development.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"4 ","pages":"Article 100107"},"PeriodicalIF":0.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145610632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Graminoides A-D, antibacterial cyclic octaketides from the desert-derived Streptomyces","authors":"Xianggang Hu ,&nbsp;Shengliang Zhao ,&nbsp;Wenqing Yan ,&nbsp;Qian Zhang ,&nbsp;Jie Huang ,&nbsp;Lei Dong ,&nbsp;Chunhua Lu ,&nbsp;Wenjun Li","doi":"10.1016/j.pscia.2025.100106","DOIUrl":"10.1016/j.pscia.2025.100106","url":null,"abstract":"<div><div>Four previously unreported cyclic octaketides, designated as graminotides A-D (<strong>1</strong>–<strong>4</strong>), along with the known compound GTRI-02 (<strong>5</strong>), were isolated from the desert soil-derived actinomycete <em>Streptomyces graminisoli</em> SD11. The planar structures of <strong>1</strong>–<strong>4</strong> were elucidated through comprehensive spectroscopic analysis including 1D, 2D NMR techniques coupled with HR-ESI-MS measurements. The absolute configurations were established through combination of NOE and coupling constants analysis, and comparison the experimental and calculated ECD spectra. Notably, the biological evaluation revealed that <strong>1</strong> and <strong>2</strong> showed moderate antibacterial activity against <em>Staphylococcus aureus</em> ATCC25923 with MIC of 64 and 32 μg/mL, while <strong>3</strong> displayed activity against <em>Proteus vulgaris</em> CPCC160013 with MIC of 64 μg/mL, respectively. None of the isolated compounds showed antiproliferative effects against HepG2 and MDA-MB-231 cells at a tested concentration of 30 μM.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"4 ","pages":"Article 100106"},"PeriodicalIF":0.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145610631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convergence of computer-aided drug discovery and artificial intelligence: Towards next-generation therapeutics","authors":"Lin Zheng ,&nbsp;Jia Cao ,&nbsp;Lanlan Jing ,&nbsp;Dongwei Kang ,&nbsp;Zhao Wang ,&nbsp;Xinyong Liu","doi":"10.1016/j.pscia.2025.100100","DOIUrl":"10.1016/j.pscia.2025.100100","url":null,"abstract":"<div><div>The field of drug discovery has undergone transformative changes with the rapid advancement of computing technology. Both academia and the pharmaceutical industry are increasingly adopting computational approaches, with computer-aided drug discovery (CADD) enhancing researchers’ ability to develop cost-effective and resource-efficient solutions. Advances in computational power enable us to explore chemical spaces beyond human capabilities, construct extensive compound libraries, and efficiently predict molecular physicochemical properties and biological activities. Furthermore, artificial intelligence (AI) is now deeply integrated throughout the drug discovery process. As an advanced methodology within CADD, AI-driven drug design (AIDD) accelerates critical stages, including target identification, candidate screening, pharmacological evaluation, and quality control. This approach not only shortens development timelines but also reduces research risks and costs. However, translating computational results for small molecules into successful wet-lab experiments often proves more complex than anticipated, and CADD development still faces persistent constraints. With the evolution of AI tools and the maturation of emerging technologies, CADD holds promise for driving deeper transformations in drug development.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"4 ","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145610633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational screening of Sophora flavescens phytochemicals as potential aromatase inhibitors: Molecular docking, ADMET, Network pharmacology, Molecular dynamics simulation, and DFT studies","authors":"Laiba Rashid ,&nbsp;Jarin Tasnim ,&nbsp;Md Mehedi Hasan ,&nbsp;Hammad Ismail ,&nbsp;Khan Rajib Hossain ,&nbsp;Sarnop Sarker ,&nbsp;Ayesha Younas ,&nbsp;Muhammad Mujtaba ,&nbsp;Mohammad Taufiq Alam","doi":"10.1016/j.pscia.2026.100108","DOIUrl":"10.1016/j.pscia.2026.100108","url":null,"abstract":"<div><div>Breast cancer is one of the most prominent types of cancers and a leading cause of fatality in women throughout the world. It also contributes to abnormal estrogen production. The enzyme aromatase (CYP19A1), which catalyzes estrogen biosynthesis, regulates hormone-dependent breast cancer. Therefore, it is used as a therapeutic target in breast cancer therapy. However, long-term usage of FDA-approved aromatase inhibitors, i.e., Letrozole and Anastrozole, in women demonstrates several adverse effects. Thus, the study was conducted to identify safer, natural alternatives using an integrated computational method. In the initial screening, more than 70 phytochemicals from the <em>Sophora flavescens</em> plant were docked against aromatase (PDB ID: 3EQM) using PyRx. Though Artocarpin SF02 showed the highest binding affinity among these phytochemicals (−10.1 kcal/mol), it had the highest toxicity to the immune system and the lowest LD50 value compared to SF03. So SF04 Vogelin E, having a binding affinity of (−9.3 kcal/mol), followed by its good pharmacokinetic &amp; toxicity profile. Network pharmacology revealed that it interacts with targets of interest, including CYP19A1, ESR1, and EGFR, which regulate estrogen biosynthesis, as well as PI3K-Akt and MAPK signaling pathways, in breast cancer development. The stability of the aromatase-Vogelin E complex was confirmed by performing MD simulations with GROMACS 2022.4 using the CHARMM36 force field and TIP3P water model, which predicted stable complex formation over the 100 ns trajectory. To further validate the chemical stability and electronic reactivity of the selected compound, DFT calculations were performed using Gaussian 09 with the B3LYP/6-31G basis set. These findings suggest that a flavonoid-based derivative, Vogelin E, derived from the <em>Sophora flavescens</em> plant may be a highly effective, safe, and natural aromatase inhibitor. This research offers a good prospect for in vitro and in vivo research to develop alternative therapies to be used in hormone-dependent breast cancer.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"4 ","pages":"Article 100108"},"PeriodicalIF":0.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of 3D printing technology in the field of oral materials","authors":"Khan Rajib Hossain ,&nbsp;Dipika Ramdas Kalambhe ,&nbsp;M. Abdul Jalil ,&nbsp;Nusrat Tabassum Farah","doi":"10.1016/j.pscia.2025.100093","DOIUrl":"10.1016/j.pscia.2025.100093","url":null,"abstract":"<div><div>The emergence of three-dimensional (3D) printing has represented a significant technological breakthrough, exerting a profound influence across various domains of society in recent times. There has been a noticeable shift in the healthcare industry's dominant paradigm of therapeutic interventions, particularly regarding the utilization of 3D printing technology to mend or replace damaged or missing biological components. Adopting cutting-edge technology can significantly enhance the range of applications within the field of oral healthcare. A significant amount of research is being conducted to leverage the substantial potential of 3D printing in oral applications, with a focus on developing customized treatment plans tailored to specific case scenarios. By building specialized implantology from different biological composite materials layer by layer, 3D printing technology precisely restores the anatomical structure of defects in the mouth and maxillofacial region. This review presents a comprehensive discussion on the history and classification of 3D printing technology, as well as the dynamics of biological materials, cells, and bioactive factors utilized in repairing oral and maxillofacial bone defects. Additionally, this review provides an update on the materials commonly used in typical oral healthcare applications and examines future trends and concerns related to material perspectives in oral healthcare management.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assay development and screening of inhibitors targeting the SARS-CoV-2 2′-O-methyltransferase NSP16","authors":"Mengtong Cao ,&nbsp;Carl W. Trieshmann ,&nbsp;Subodh Kumar Samrat ,&nbsp;Hongmin Li ,&nbsp;Yifei Wu ,&nbsp;Steven P. Maher ,&nbsp;Angela A. Bae ,&nbsp;Zhong-Ru Xie ,&nbsp;Robert J. Hogan ,&nbsp;Y. George Zheng","doi":"10.1016/j.pscia.2025.100076","DOIUrl":"10.1016/j.pscia.2025.100076","url":null,"abstract":"<div><div>The coronavirus disease-2019 (COVID-19) pandemic, etiologically caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has profoundly impacted the global health. While vaccines have been developed, they have shown limited efficacy in treating patients already under infection or preventing infection with emerging SARS-CoV-2 variants. The nonstructural protein 16 (NSP16), with the assistance of the nonstructural protein 10 (NSP10), is responsible for forming the Cap-1 structure, which is critical for viral replication and immune evasion through the 5′-capping of viral mRNA. As a result, NSP16/NSP10 has emerged as a promising target for antiviral treatment of coronaviruses. In this study, we aimed to discover small molecule inhibitors of NSP16/NSP10 by leveraging recent structural insights and combined tools of virtual and experimental screenings. We designed a simple scintillation proximity assay to enable biochemical testing for NSP16/NSP10 enzymatic activity and applied it to screen inhibitors from candidate hit compounds that are derived from molecular docking-based virtual screenings. We identified potential hits that inhibit the NSP16 activity with cellular efficacy. Together with structural analysis and chemotype categorization, this study lays the groundwork for novel antiviral therapeutics development against SARS-CoV-2 and related coronaviruses.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100076"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Garcioligantone J and K, a pair of epimeric caged-polyprenylated xanthonoids from Garcinia Oligantha, inhibit the growth of lung cancer cells through ER stress-mediated apoptosis","authors":"Lingyu Li ,&nbsp;Hao Zheng ,&nbsp;Qingying Liu ,&nbsp;Dongmei Ren","doi":"10.1016/j.pscia.2025.100065","DOIUrl":"10.1016/j.pscia.2025.100065","url":null,"abstract":"<div><div>Garcioligantone J and K (GLJ and GLK) are a pair of isomers isolated from <em>Garcinia Oligantha</em> Merr. Herein, we described the structure elucidation including the absolute configurations of GLJ and GLK, explored and compared their anti-cancerous effects and underlying mechanism in A549 and NCI-H292 ​cells. The results indicated that GLJ and GLK are two isomers with different configuration at C-12, they inhibited cell proliferation and induced apoptosis in two lung cancer cell lines with almost the same extent. The induction of apoptosis by GLJ and GLK was demonstrated by DAPI and annexin-V-FITC/PI staining. Further investigation revealed increased Bax/Bcl-2 ratio, cleaved caspase-3, caspase-9 and PARP, loss of mitochondrial membrane potential (MMP) in cells, indicating that GLJ and GLK induced mitochondrial apoptosis. Increased GRP78, p-eIF2α and GADD153 manifested that endoplasmic reticulum (ER) stress was induced by GLJ and GLK. Meanwhile, upregulated reactive oxygen species (ROS) level was found and GLJ and GLK-induced ER stress and apoptosis could be attenuated by ROS scavenger NAC. Apoptosis induced by GLJ and GLK also could be alleviated by ER stress inhibitor 4-PBA. These showed that GLJ and GLK-induced apoptosis was mediated by ER stress relied on ROS generation. The efficacy of GLJ and GLK on lung cancer cell proliferation was further demonstrated in a zebrafish xenograft model. Collectively, the absolute configurations of GLJ and GLK were identified and they exerted lethal effects on lung cancer cells to the same extent via ROS-ER stress-mitochondrial apoptosis signaling, suggesting that GLJ and GLK might be used as potential modulating agents in lung cancer treatments.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal-organic frameworks in pharmaceutical research","authors":"Zimeng Tao ,&nbsp;Kun Hu ,&nbsp;Baoxi Zhang ,&nbsp;Shiying Yang ,&nbsp;Dezhi Yang ,&nbsp;Zhehui Zhao ,&nbsp;Li Zhang ,&nbsp;Yang Lu","doi":"10.1016/j.pscia.2025.100096","DOIUrl":"10.1016/j.pscia.2025.100096","url":null,"abstract":"<div><div>Metal-organic frameworks (MOFs) have emerged as a highly versatile class of porous materials with significant potential to advance pharmaceutical research. This review provides a comprehensive overview of the current landscape of MOFs, encompassing their synthesis strategies, characterization methodologies, and diverse biomedical applications. We detail various synthesis approaches (e.g., hydrothermal, electrochemical, microwave) and essential characterization techniques (e.g., X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) surface area analysis) that are critical for developing well-defined MOF structures. The review highlights the key advantages of MOFs in drug delivery, including their exceptional drug loading capacity, good biocompatibility, and capabilities for sustained, controlled, and targeted release. Their applications in improving drug solubility and stability, enabling pulmonary delivery, and functioning in biosensing, antimicrobial therapy, and nucleic acid delivery are also extensively discussed. Furthermore, we explore the utility of MOFs in drug structure analysis and the development of advanced functional systems, such as stimuli-responsive and self-propelled MOFs. Despite promising preclinical progress, challenges related to scalability, reproducibility, and long-term biosafety remain to be addressed for successful clinical translation. This work aims to bridge the gap between MOF materials science and pharmaceutical applications, offering valuable insights for the rational design of next-generation drug delivery systems and therapeutic platforms.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The crucial role of SPP1 in osteoporosis, osteoarthritis, and cancer","authors":"Yaru Qu ,&nbsp;Shuixian Li ,&nbsp;Huiyuan Luo ,&nbsp;Junnan Li ,&nbsp;Tong Wang ,&nbsp;Xiuzhen Han","doi":"10.1016/j.pscia.2025.100074","DOIUrl":"10.1016/j.pscia.2025.100074","url":null,"abstract":"<div><div>Osteopontin (OPN), also known as secreted phosphoprotein 1(SPP1), is a highly glycosylated and phosphorylated acidic protein, which is a multifunctional glycoprotein expressed in numerous cell types. SPP1 is involved in the attachment of osteoclasts to mineralized bone matrix, inflammatory reaction, cell recruitment, and tissue repair, and plays an important role in bone formation, fibrosis, immune diseases, and cancer. The role of SPP1 in osteoporosis, osteoarthritis and cancer is multi-faceted. While it holds potential therapeutic value, it also presents certain limitations. This review integrates the molecular structural characteristics of SPP1, including isoform variants and post-translational modifications, with its pathophysiological functions. It highlights the regulatory roles of SPP1 in these diseases: maintaining the dynamic balance between bone resorption and formation in osteoporosis, promoting cartilage degeneration and inflammation in osteoarthritis, and driving tumor progression in cancer through the activation of pathways such as PI3K/AKT/mTOR. Furthermore, SPP1 regulates tumor-associated macrophages and fibroblasts within the tumor microenvironment, thereby facilitating immune evasion and metastasis. The article also underscores the potential value of precisely modulating SPP1 activity in the treatment of osteoporosis and osteoarthritis and suggests a combined therapeutic strategy targeting SPP1, offering novel insights into overcoming the limitations of single-target cancer therapies.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100074"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microdynamic flowability for early API characterisation: A case study on Palbociclib","authors":"David Blanco ,&nbsp;Nicolas Pätzmann ,&nbsp;Pablo García-Triñanes","doi":"10.1016/j.pscia.2025.100069","DOIUrl":"10.1016/j.pscia.2025.100069","url":null,"abstract":"<div><div>This study explores microdynamic flowability as an innovative approach for early active pharmaceutical ingredient (API) characterisation, when compounds are often scarce and/or expensive. By incorporating small-scale flow measurements during the pre-formulation stage, we aim to support strategic decision-making in formulation development and process design. Laboratory-scale micronisation of the poorly water-soluble drug Palbociclib, while enhancing dissolution, was found to adversely affect flowability. Agglomeration driven by cohesive forces was quantitatively described for the first time via image analysis using sample quantities of less than 200 mg. Our findings demonstrate that microdynamic flow studies provide critical insights into the processability of APIs under low-stress conditions, such as those relevant to research and development (R&amp;D) tablet presses. These results highlight the value of advanced flowability analysis in early-stage development, enabling improved understanding and control of powder processing in pharmaceutical manufacturing and particle engineering.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}