Pharmaceuticals最新文献

{"title":"Bioactive-Enriched Chitosan/Poly(vinyl Alcohol) Electrospun Nanofibers for Wound Healing: In Vitro and In Vivo Evaluation.","authors":"Teodora Iurascu, Andreea-Teodora Iacob, Carmen Solcan, Cristina Mariana Uritu, Bianca-Stefania Profire, Narcisa Laura Marangoci, Adina Coroaba, Andrei Szilagyi, Ivona Costachescu, Maria-Raluca Gogu, Leontina-Elena Filipiuc, Lenuta Profire","doi":"10.3390/ph19040581","DOIUrl":"10.3390/ph19040581","url":null,"abstract":"<p><p><b>Background:</b> Wound healing remains a major clinical challenge, often impaired by persistent inflammation, oxidative stress, and abnormal extracellular matrix remodeling. Electrospun nanofibers (NFs) have emerged as promising wound dressing platforms due to their biomimetic structure and capacity to incorporate multiple bioactive compounds (ACs) with synergistic therapeutic effects. <b>Objectives:</b> This study aimed to biologically assess novel chitosan/poly(vinyl alcohol) (CH/PVA) NFs functionalized with natural active compounds (L-arginine-ARG, allantoin-ALA, royal jelly-RJ, and curcumin-CUR) as multifunctional systems for wound healing and tissue remodeling. <b>Methods:</b> The nanofibrous systems performed the in vitro evaluation of antioxidant activity (DPPH, ABTS, FRAP, PRAP), anti-inflammatory potential (protein denaturation test), hemocompatibility, and cytocompatibility using dermal fibroblasts. In vivo healing performance was evaluated in an excisional wound model using macroscopic wound contraction analysis, histopathology, and immunohistochemical staining (MMP-9, CD31, VEGF-A, α-SMA). <b>Results:</b> The bioactive-enriched CH/PVA NFs exhibited strong antioxidant and anti-inflammatory activity, excellent hemocompatibility (hemolysis < 5%), and excellent cytocompatibility, with promoting fibroblast proliferation. In vivo experiments revealed that the treated groups exhibited accelerated wound closure, improved re-epithelialization, increased angiogenesis, and showed more efficient tissue remodeling compared to the controls, as validated by histological and immunohistochemical studies. <b>Conclusions:</b> The findings indicate that bioactive-enriched CH/PVA NFs serve as effective, biocompatible, and multifunctional matrices for wound healing, hence endorsing their potential for further translational advancement in skin regeneration applications.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kaempferol-7-O-Glucoside Ameliorates Atopic Dermatitis via the TSLP-Mediated JAK2/STAT5 Signaling Axis.","authors":"Xingmei Lan, Jing Liu, Yijie Shi, Yonghua Zhou, Cheng Yang, Bingtian Zhao","doi":"10.3390/ph19040580","DOIUrl":"10.3390/ph19040580","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Thymic stromal lymphopoietin (TSLP) is central to the pathogenesis of atopic dermatitis (AD) and a promising therapeutic target. However, developing small-molecule TSLP inhibitors is challenging due to the difficulty in disrupting the TSLP-TSLPR interface. This study aimed to explore naturally sourced blockers of the TSLP-TSLPR interaction and identify novel candidate compounds for AD treatment. <b>Methods:</b> HuT78 cells were stimulated with PMA, ionomycin, and TSLP to establish an AD model. Inflammatory cytokines were measured by qRT-PCR and ELISA. JAK/STAT signaling was analyzed by Western blot. In female BALB/c mice, DNCB-induced AD-like skin lesions were topically treated with test compounds, followed by histopathological and immunohistochemical assessment. <b>Results:</b> Eight compounds were screened, and their key structural features were elucidated via structure-activity relationship (SAR) analysis. Among them, kaempferol-7-O-glucoside (K-7-G) emerged as the most potent candidate. It interfered with the TSLP-TSLPR interaction, selectively inhibited TSLP-mediated JAK2/STAT5 phosphorylation, and significantly downregulated IL-4 (<i>p</i> < 0.0001) and IL-13 (<i>p</i> < 0.001) levels. Topical application of 1% K-7-G significantly alleviated AD-like symptoms in a mouse model, decreasing dorsal skin thickness, dermatitis score, and scratching frequency while restoring the expression of filaggrin, loricrin, and occludin (<i>p</i> < 0.0001). Meanwhile, it significantly reduced key inflammatory mediators in a concentration-dependent manner, including TSLP, IL-4, IL-13, TNF-α, IFN-γ, and IgE. <b>Conclusions:</b> This study demonstrates that K-7-G is a novel natural TSLP inhibitor capable of blocking the TSLP-TSLPR signaling pathway and effectively improving AD symptoms. Further research may explore its therapeutic potential in other inflammatory diseases.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esculetin Attenuates Inflammation and Fibrosis to Prevent AKI-to-CKD Transition in Adenine-Induced Renal Injury by Inhibiting the EGFR/SRC/PI3K/AKT/NF-κB Signaling Axis.","authors":"Jianglong Chen, Bin Xia, Rujie Zhou, Yunfei Cui, Yu Zhu, Meijia Chen, Jinhua Su, Jinhui Wang, Guang Li","doi":"10.3390/ph19040578","DOIUrl":"10.3390/ph19040578","url":null,"abstract":"<p><p><b>Background:</b> Chronic kidney disease (CKD) is characterized by irreversible structural damage and functional deterioration of the kidneys. Esculetin (ES), with its anti-inflammatory, antioxidant, and immunomodulatory activities, shows potential in delaying renal function decline. This study aimed to investigate the protective effect of ES on adenine-induced CKD in mice and its underlying molecular mechanism, with a focus on its role in preventing the transition from acute kidney injury (AKI) to CKD. <b>Methods:</b> A AKI-to-CKD transition mice model was established by feeding mice a 0.2% adenine diet, and ES (30, 60 mg/kg) was co-administered for 4 weeks as a prophylactic intervention. Serum creatinine (SCr), blood urea nitrogen (BUN), and renal histopathology (HE, Masson, IHC) were evaluated to assess renal injury. Network pharmacology and transcriptomics were combined to screen the targets, and Western blot was used to verify the signaling pathways. <b>Results:</b> ES significantly reduced SCr and BUN levels in CKD mice and alleviated renal tubular dilation and inflammatory infiltration. ES decreased pro-inflammatory factors (IL-1β, IL-6, TNF-α) and MDA levels and enhanced SOD activity. Additionally, ES inhibited renal interstitial collagen deposition and reversed epithelial-mesenchymal transition (EMT) by upregulating E-cadherin and downregulating α-SMA levels. Mechanism studies confirmed that ES significantly inhibited the phosphorylation levels of p-EGFR, p-SRC, p-PI3K, p-AKT, and p-p65 in renal tissues. <b>Conclusions:</b> ES effectively inhibits inflammation, oxidative stress, and fibrosis by modulating the EGFR/SRC/PI3K/AKT/NF-κB signaling axis, thereby preventing the AKI-to-CKD transition in the adenine-induced renal injury model and alleviating the progression of chronic renal damage.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-Induced Amyloid-Related Imaging Abnormalities: A Neurovascular Perspective on Risk Assessment.","authors":"Marialuisa Zedde, Mattia Losa, Andrea Donniaquio, Ilaria Gandoglia, Massimo Del Sette, Luca Roccatagliata, Fabrizio Piazza, Matteo Pardini, Rosario Pascarella","doi":"10.3390/ph19040579","DOIUrl":"10.3390/ph19040579","url":null,"abstract":"<p><strong>Background: </strong>Anti-amyloid therapies (AAT) are reshaping the therapeutic landscape of Alzheimer's disease (AD), yet their implementation remains constrained by the risk of amyloid-related imaging abnormalities (ARIA). Although the ARIA phenomenon is well recognized, most available evidence stems from clinical trial safety reports framed predominantly from a dementia-oriented perspective, with relatively limited integration of vascular neurology principles.</p><p><strong>Methods: </strong>In this narrative review, we examine drug-induced ARIA through a neurovascular lens, highlighting how cerebrovascular comorbidity, particularly cerebral amyloid angiopathy (CAA), influences the risk and severity of ARIA.</p><p><strong>Results: </strong>We critically evaluated how CAA comorbidity has been assessed in randomized controlled trials, focusing on exclusion criteria, imaging thresholds, and the resulting implications for external validity. Finally, we evaluated current approaches to ARIA risk stratification and proposed a more integrative framework that combines vascular imaging markers, APOE ε4 genotype, and key clinical comorbidities.</p><p><strong>Conclusions: </strong>A more tailored patient selection and monitoring strategies may ultimately improve real-world outcomes and optimize resources in the era of AAT.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Luciferase-Based In Vitro Assay to Evaluate the Efficacy of Anti-Cryptosporidial Drugs Against <i>Cryptosporidium parvum</i>.","authors":"Rie Kubota, Coh-Ichi Nihei, Yoshifumi Nishikawa","doi":"10.3390/ph19040576","DOIUrl":"10.3390/ph19040576","url":null,"abstract":"<p><p><b>Background/Objectives</b>: <i>Cryptosporidium parvum</i> is a major causative agent of cryptosporidiosis; however, progress in anti-cryptosporidial drug discovery has been hindered by the lack of robust and reproducible in vitro evaluation systems. In this study, we developed and optimized a luciferase-based in vitro assay to quantitatively monitor <i>C. parvum</i> growth in HCT-8 cells. <b>Methods</b>: Key experimental parameters affecting infection efficiency were systematically examined, including sodium taurocholate treatment, timing of medium replacement, and serum concentration. <b>Results</b>: Sodium taurocholate significantly enhanced parasite infectivity, and removal of non-invaded parasites at 3 h post-infection (hpi) resulted in approximately 2-fold and 3.7-fold increase in luciferase activity at 24 and 48 hpi, respectively, compared with untreated controls. In contrast, removal at 24 hpi led to only an approximately 2.5-fold increase at 48 hpi, consistent with stage-dependent differences in parasite development. Morphological analyses confirmed parasite differentiation from trophozoites to meronts, followed by progression toward sexual stages. Using the optimized assay system, we evaluated several anticoccidial compounds and demonstrated potent in vitro activity of monensin and its structural analog kijimicin, whereas diclazuril and toltrazuril exhibited limited efficacy. <b>Conclusions</b>: Collectively, this luciferase-based platform provides a reliable and quantitative tool for anti-cryptosporidial drug screening and will facilitate future therapeutic development against <i>C. parvum</i>.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Formulation-Dependent Chemical Variation and Comparability of Maziren-Wan Preparations via Multi-Component LC-MS/MS Profiling.","authors":"Chang-Seob Seo","doi":"10.3390/ph19040577","DOIUrl":"10.3390/ph19040577","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Maziren-Wan (MZRW) is a traditional herbal prescription that has been used for the treatment of chronic constipation and is currently available in the form of granules or decoctions. Given its multi-component nature and various dosage forms, evaluating the chemical consistency of MZRW preparations is important for pharmaceutical quality assessment. The aim of the present study was to compare formulation-dependent chemical profiles of different MZRW preparations using a multi-component analytical approach. <b>Methods</b>: An excipient-free reference extract and two commercially available MZRW extract granule products were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method operating in multiple reaction monitoring mode. Thirty marker compounds derived from the constituent herbs were simultaneously quantified, and their levels were statistically compared among the preparations. <b>Results</b>: Quantitative analysis revealed formulation-dependent variation in the abundance of several marker compounds. Amygdalin and magnoloside A exhibited markedly higher levels in the excipient-free reference extract than in the commercial granule products, whereas sennoside A showed relatively consistent levels across the preparations. <b>Conclusions</b>: The results indicate that MZRW preparations sharing an identical herbal composition can exhibit formulation-dependent differences in chemical profiles. Comparative evaluation based on multiple marker compounds may provide useful information for assessing chemical consistency and supporting quality assessment of MZRW preparations formulated under different conditions.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological Potential and Physicochemical Properties of Ionic Liquids Bioinspired by Carboxylic Acids: A Review.","authors":"Carmen Terán, Marta María Mato, Pedro Besada","doi":"10.3390/ph19040570","DOIUrl":"10.3390/ph19040570","url":null,"abstract":"<p><p>Ionic liquids (ILs) derived from bioactive compounds have emerged as a versatile and highly tunable platform for designing novel functional materials with biomedical applications. Many of these systems incorporate naturally occurring carboxylate anions of relevance to medicinal chemistry, biotechnology, and biomedicine, which has intensified interest in this family of bioinspired ILs. This review focuses on ILs derived from carboxylic acids of natural origin, including fatty acids, phenolic acids, and hydroxy acids, and highlights recent advances in their design, bioactivity, and physicochemical characterization, with particular emphasis on systems based on biocompatible components. Additionally, it addresses synthetic strategies, toxicological aspects, and biological potential. Key physicochemical properties discussed include thermal stability, glass transition temperatures, melting and crystallization points, viscosity, density, solubility, refractive index, polarity, and amphiphilic behavior.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenosides Rb3 and Rc Exhibit Anti-Amoebic Activities Against <i>Naegleria fowleri</i>, the Etiological Agent of Primary Amoebic Meningoencephalitis.","authors":"Thu Hằng Nguyễn, Hương Giang Lê, Tuấn Cường Võ, Minkyoung Cho, Byoung-Kuk Na","doi":"10.3390/ph19040573","DOIUrl":"10.3390/ph19040573","url":null,"abstract":"<p><p><b>Background/Objectives:</b><i>Naegleria fowleri</i> is an opportunistic pathogen causing primary amoebic meningoencephalitis (PAM), a fatal neuroinflammatory disease with a high mortality rate of over 97%, in humans. Currently, there are no approved therapeutics for PAM, underscoring the urgent necessity of developing effective and safe drugs. This study aimed to evaluate the potential of ginsenosides Rb3 and Rc as alternative or supplementary drug candidates for PAM by assessing their anti-amoebic activities against <i>N. fowleri</i>. <b>Methods:</b> Anti-<i>N. fowleri</i> activities of ginsenosides Rb3 and Rc and their cytotoxicity to C6 glial cells were evaluated by cell viability assay. The underlying anti-amoebic mode of action of Rb3 and Rc was analyzed by a series of assays for apoptosis-necrosis, TUNEL, intracellular reactive oxygen species (ROS), mitochondrial dysfunction, ATP production, caspase-3, and autophagy. The expression profiles of apoptosis- and autophagy-related genes were also analyzed. <b>Results:</b> Rb3 and Rc effectively induced death of <i>N. fowleri</i> trophozoites with IC₅₀ values of 94.71 ± 1.63 μM and 126.99 ± 1.88 μM, respectively. However, Rb3 and Rc showed no significant cytotoxicities against C6 glial cells, suggesting their selective anti-<i>N. fowleri</i> activities. Typical apoptosis signals, such as apopxin staining and DNA fragmentation, were detected in amoebae upon treatment with Rb3 or Rc. These two ginsenosides enhanced ROS production and induced mitochondrial dysfunction in the amoebae. Enhanced caspase-3 activity and autophagy formation were also identified in amoebae treated with Rb3 or Rc. <b>Conclusions:</b> These results provide the first evidence that ginsenosides Rb3 and Rc induce apoptosis-like programmed cell death in <i>N. fowleri</i>, suggesting that they are potential candidates in developing novel therapeutic strategies against PAM.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Doxorubicin Delivery Using TPP-Folate-Dendrimer-Functionalized Gold Nanoclusters.","authors":"Mkhuseli Zenze, Moganavelli Singh","doi":"10.3390/ph19040572","DOIUrl":"10.3390/ph19040572","url":null,"abstract":"<p><p><b>Background</b>: Cancer is a major health concern that significantly impacts the global population. Selective chemotherapeutic delivery is needed to improve the efficacy of cancer therapy while minimizing side effects in healthy cells. This study investigated the potential of gold nanoclusters (AuNCs) functionalized with poly(amidoamine) dendrimers (PAMAM) and folic acid (FA) to selectively deliver doxorubicin (DOX) to cancer cells that express the folate receptor (FR). <b>Methods</b>: AuNC synthesis was confirmed via UV-visible and Fourier transform infrared spectroscopy, nanoparticle tracking analysis, and transmission electron microscopy. Folic acid (FA) was incorporated for cell surface receptor targeting, while the triphenylphosphonium cation (TPP⁺) was added to improve mitochondrial localization. Cytotoxicity (MTT), apoptosis, caspase 3/7, mitopotential, and oxidative stress assays were assessed using human MCF-7 (breast adenocarcinoma), HeLa (cervical carcinoma), Caco-2 (colon adenocarcinoma), MDA-MB-231 (epithelial breast cancer), and the embryonic kidney (HEK293) cells. <b>Results</b>: Favorable DOX loading (>78%), with more than 90% of the drug released at pH 4.5, was achieved. A dose-dependent increase in cytotoxicity was observed, with IC50 values lower in cancer cells than HEK293 cells, indicating selective toxicity and minimal off-target effects. Targeting nanocomplexes produced the best responses in the mitopotential, caspase, and oxidative stress assays in HeLa and MCF-7 cells. <b>Conclusions</b>: The improved cytotoxicity in cancer cells may be due to folate-receptor-mediated cellular uptake, as well as the mitochondrial uptake of TPP⁺ nanocomplexes. This highlighted the potential of the drug-AuNC nanocomplexes to limit systemic side effects, proposing a potential novel strategy for drug delivery to cancer cells.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Potential of Organotin(IV) Carbodithioate Derivatives with Vitamins D and E in MCF-7 and MDA-MB-231 Breast Cancer Cells.","authors":"Balquees Kanwal, Farzana Shaheen, Syeda Saba Shah, Yasmeen Cheema, Saqib Ali, Rumeza Hanif","doi":"10.3390/ph19040571","DOIUrl":"10.3390/ph19040571","url":null,"abstract":"<p><p><b>Background</b>: Breast cancer (BC) remains the most prevalent malignancy among women worldwide, with one in eight at risk during their lifetime. Platinum-based chemotherapeutic drugs, despite of their binding to the DNA of cancer cells, are plagued by toxicity and resistance, necessitating the need for safer and more effective alternatives, such as organometallic complexes. Both synthetic organometallic complexes and natural compounds have attracted attention in this regard. Organotin(IV) complexes are promising chemotherapeutics due to their structural versatility and bioactivity, while vitamins such as Vitamin D (VD) and Vitamin E (VE) exhibit antiproliferative, anti-inflammatory, and antioxidant properties, making them valuable candidates for combination therapy. <b>Methodology</b>: In this study, six novel organotin(IV) dithiocarbamate complexes [LMe₃Sn (Complex 1), LBu₃Sn (Complex 2), LPh₃Sn (Complex 3), LMe₂SnCl (Complex 4), LBu₂SnCl (Complex 5), and L₂Me₂Sn (Complex 6), where L = (E)-4-styrylpiperazine-1-carbodithioate], were synthesized and characterized by FT-IR, ¹H-, ¹³C-NMR, and elemental analysis. <b>Results</b>: Structural studies confirmed penta- and hexacoordination geometries. In silico docking against six BC-related proteins identified Complexes 2 and 4 with both vitamins as promising candidates, exhibiting strong binding affinities, with stable interaction profiles. However, integration of pharmacokinetic, antioxidant, and anti-inflammatory analyses highlighted Complex 4 with both vitamins as the most potent candidate owing to its superior ADME characteristics and balanced biological properties. Subsequent in vitro assays confirmed these findings, as Complex 4 demonstrated strong cytotoxic activity against both MCF-7 (>1.16-fold) and MDA-MB-231 (>1.46-fold) cell lines, surpassing the efficacy of cisplatin. Remarkably, co-administration of VD or VE with Complex 4 further enhanced its anticancer potential, with Chou-Talalay combination index values < 1 (0.66-0.91) indicating a synergistic interaction. <b>Conclusions</b>: Collectively, these results identify Complex 4 as a promising lead compound, and its synergistic activity with natural vitamins may promote cell death, likely through apoptosis induction and modulation of oxidative stress, underscoring its potential as an effective and less toxic therapeutic strategy for breast cancer management.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}