Pakistan journal of pharmaceutical sciences最新文献

{"title":"Short-term comparative effects of semaglutide, either alone or in conjunction with canagliflozin, on early diabetic kidney disease.","authors":"Wang Long, Li Ningning, Huang Weijun","doi":"10.36721/PJPS.2026.39.7.204.1","DOIUrl":"10.36721/PJPS.2026.39.7.204.1","url":null,"abstract":"<p><strong>Background: </strong>Diabetic kidney disease (DKD) is a common complication of type 2 diabetes mellitus and an important cause of end-stage renal disease. Metabolic dysfunction, albuminuria, and chronic low-grade inflammation characterize early DKD, leading to progressive renal impairment. To date, SGLT2 inhibitors and GLP-1 receptor agonists are known to provide renoprotective and metabolic benefits; however, there is limited evidence available regarding the combined use of these treatments in early DKD.</p><p><strong>Objectives: </strong>This study evaluated the short-term effects of canagliflozin and semaglutide, administered alone or in combination, on renal function, metabolic parameters, and systemic inflammatory markers in patients with early-stage DKD.</p><p><strong>Methods: </strong>In this randomized controlled trial, 120 patients with early-stage diabetic kidney disease were randomly allocated (1:1:1:1) to four groups (n = 30 each): canagliflozin (100 mg orally once daily), semaglutide (0.25 mg once weekly with escalation to 1.0 mg after 4 weeks), combination treatment, or placebo/control.</p><p><strong>Participants: </strong>All participants were provided standard background care. Treatment continued for 24 weeks. The main renal outcomes were urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Glycemic control, insulin resistance, lipid parameters, and inflammatory biomarkers (HbA1c, fasting glucose, HOMA-IR, TNF-α, IL-6, CRP) were considered as secondary outcomes. Safety assessment was conducted using binary safety assessment.</p><p><strong>Results: </strong>At 24 weeks, combination therapy achieved significantly greater reductions in UACR compared with monotherapy and placebo (P < 0.05). Across treatment groups, a small reduction in eGFR was observed without significant between-group differences. Measurements of HbA1c, fasting glucose, HOMA-IR, lipid parameters, and inflammatory markers showed better results in the combination therapy group compared to single-agent therapy (P < 0.05). Rates of adverse events were similar between the groups.</p><p><strong>Conclusion: </strong>Combined canagliflozin and semaglutide therapy demonstrated superior short-term benefits in reducing albuminuria, improving metabolic control, and attenuating systemic inflammation in early DKD, supporting further long-term evaluation of renal and cardiovascular outcomes.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 7","pages":"2165-2172"},"PeriodicalIF":0.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR9 agonists alleviate diabetic condition by promoting the maturation of differentiated bone marrow mesenchymal stem cells in rats.","authors":"Chuan Liu, Huayong Zheng, Peng Lu, Jing Tian, Yenuan Hu, Li Yao, Tiansheng Sun","doi":"10.36721/PJPS.2026.39.7.205.1","DOIUrl":"10.36721/PJPS.2026.39.7.205.1","url":null,"abstract":"<p><strong>Background: </strong>Current diabetes therapies often fail to address the loss of insulin-producing β-cells. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into insulin-producing cells (IPCs), but functional maturity remains limited. Toll-like receptor 9 (TLR9) agonists may enhance BMSC maturation.</p><p><strong>Objectives: </strong>To investigate the ability of TLR9 agonists to promote the maturation of BMSCs in diabetic rats.</p><p><strong>Methods: </strong>BMSCs were isolated from rat bone marrow and identified by trilineage differentiation tests and flow cytometry. BMSCs were then differentiated into IPCs and treated with different concentrations of TLR9 agonists. PCR detected transcriptional levels of pancreatic endocrine-related genes. Diabetic model in rats was established using streptozotocin. BMSCs were encapsulated in TheraCyte capsules and subcutaneously transplanted into diabetic rats. Intraperitoneal injection of TLR9 agonists was performed, with serum insulin, C-peptide and fasting blood glucose (FBG) levels monitored in the transplanted rats. The recovered BMSCs were further characterized by immunofluorescence staining after the rats were killed.</p><p><strong>Results: </strong>Differentiated BMSCs displayed characteristics of IPCs, such as the ability to secrete insulin and C-peptide in vitro. Further, when exposed to gradient concentrations of TLR9 agonists, differentiated MSCs exhibited enhanced expression of pancreatic-associated endocrine genes and transcription factor levels. In vivo, differentiated BMSC transplantation combined with TLR9 agonist administration notably improved diabetic conditions, as evidenced by suppressed FBG levels and elevated serum insulin and C-peptide levels, comparable to those in the normal group. However, withdrawal of TLR9 agonists attenuated the therapeutic effects. Finally, immunofluorescence staining confirmed that a TLR9 agonist promoted IPC maturation, as evidenced by co-expression of insulin and C-peptide in vivo.</p><p><strong>Conclusion: </strong>TLR9 agonists promote the differentiation and functional maturation of BMSCs into IPCs, thereby improving metabolic parameters in diabetic rats. This \"stem cell-immunomodulator\" strategy provides a foundation for developing functional β-cell replacement therapies.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 7","pages":"2173-2189"},"PeriodicalIF":0.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunity-oriented drug strategies for viral encephalitis: Acyclovir, antiepileptics and corticosteroids in neurological intensive care.","authors":"Liping Yu, Cheng Liang","doi":"10.36721/PJPS.2026.39.7.199.1","DOIUrl":"10.36721/PJPS.2026.39.7.199.1","url":null,"abstract":"<p><p>Viral encephalitis (VE), is a life-threatening neurological disorder marked by inflammation of brain parenchyma, driven by direct viral cytotoxicity and host immune-mediated injury. Globally, its incidence ranges from 1.4 to 13.8 cases per 100,000 individuals annually, with significant morbidity and mortality in endemic regions such as India, among children. Neurotropic viruses including herpes simplex virus (HSV), Japanese encephalitis virus (JEV) and West Nile virus, enter central nervous system via hematogenous or neuronal routes, triggering viral replication, cytokine release and blood-brain barrier disruption, resulting in seizures, cerebral edema and long-term neurological deficits. Current management in neurological intensive care relies on immunity-oriented strategies: Acyclovir as first-line antiviral for HSV and varicella-zoster virus, antiepileptics to control seizures and limit secondary neuronal injury and corticosteroids to modulate harmful neuroinflammation and cerebral edema. Emerging therapies, including novel antivirals (favipiravir, remdesivir, brincidofovir), monoclonal antibodies, cytokine inhibitors (tocilizumab, anakinra) and B-cell/plasma cell-targeted agents (rituximab, daratumumab), offer promise by simultaneously addressing viral replication and immune dysregulation. Personalized biomarker-guided integrating pathogen-directed and host-targeted therapies may optimize outcomes, reduce neuronal injury and improve recovery. This review underscores the importance of a multidimensional, immunity-oriented treatment paradigm, highlighting both established and emerging strategies to enhance prognosis and long-term neurological functions in patients with viral encephalitis.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 7","pages":"2108-2119"},"PeriodicalIF":0.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analysis of single-cell and bulk-RNA sequencing data reveals drug therapeutic targets and prognostic biomarkers related to ribosome biogenesis in hepatocellular carcinoma.","authors":"Anjing Zhao, Jinglian Zheng, Jingjing Feng, Xiaoqu Zhu, Linrong Zhu, Qianqian Hu, Chunming Wu","doi":"10.36721/PJPS.2026.39.7.187.1","DOIUrl":"10.36721/PJPS.2026.39.7.187.1","url":null,"abstract":"<p><strong>Background: </strong>Ribosome biogenesis is involved in the progression of hepatocellular carcinoma (HCC), but the specific mechanisms and diagnostic values of ribosome biogenesis-related genes (RBRGs) in HCC remain unclear.</p><p><strong>Objectives: </strong>We aimed to explore potential therapeutic targets in HCC from RBRGs.</p><p><strong>Methods: </strong>The differentially expressed RBRGs (DE-RBRGs) were explored using publicly available bulk RNA-sequencing data. Cox regression analysis was employed to evaluate the prognostic significance of the DE‑RBRGs. The optimal machine learning algorithm was selected to construct a prognostic model. The predictive performance of the model was assessed using Kaplan‑Meier analysis and receiver operating characteristic (ROC) curves. Single‑cell RNA‑sequencing data were subsequently utilized to identify key cell populations and the corresponding DE‑RBRGs.</p><p><strong>Results: </strong>Bioinformatics analyses revealed 88 DE-RBRGs, predominantly enriched in ribosome biogenesis-related functions and pathways. The univariate Cox regression identified 12 DE-RBRGs with prognostic values. Following, the optimal machine learning algorithm (StepCox [forward] + SuperPC) was selected to construct a prognostic model. Survival analysis demonstrated that patients in the low-risk group exhibited markedly prolonged lifespan relative to their high-risk counterparts. ROC curves confirmed the predictive accuracy of this prognostic model in both training and validation cohorts. These 12 DE-RBRGs were significantly associated with immune cell infiltration, tumor immune evasion and drug sensitivity. Analysis of single-cell sequencing data identified hepatocytes as central mediators of HCC pathogenesis, which was associated with high expression of two DE-RBRGs: Nucleophosmin 1 (NPM1) and Ras-Related Nuclear Protein (RAN).</p><p><strong>Conclusion: </strong>NPM1 and RAN, which are highly expressed in hepatocytes, may serve as potential therapeutic targets in HCC. Their established roles in ribosome biogenesis could drive the development of novel therapies targeting this pathway.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 7","pages":"1964-1976"},"PeriodicalIF":0.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological synthesis of silver nanoparticles using extracts from Citrullus colocynthis and their anticancer activity.","authors":"Nehad S Alsubhi","doi":"10.36721/PJPS.2026.39.7.206.1","DOIUrl":"10.36721/PJPS.2026.39.7.206.1","url":null,"abstract":"<p><strong>Background: </strong>Green synthesis of silver nanoparticles (AgNPs) using plant extract has emerged as an eco-friendly alternative to conventional chemical methods, offering potential biomedical applications, particularly in cancer therapy.</p><p><strong>Objectives: </strong>This study aimed to synthesize AgNPs from extracts of Citrullus colocynthis leaves, stems and seeds and to evaluate their cytotoxic effects against selected cancer cell lines.</p><p><strong>Methods: </strong>AgNPs were biosynthesized using plant extract and characterized using standard analytic techniques. The cytotoxic activity of the synthesized nanoparticles was assessed against A549, HCT116 and MCF-7 cancer cell lines.</p><p><strong>Results: </strong>the biosynthesis of AgNPs demonstrated significant anti-cancer activity, with leaf-derived AgNPs showing the strongest cytotoxic effect. Notably, to our knowledge, this study is the first to evaluate leave-derived AgNPs against A549 cells.</p><p><strong>Conclusion: </strong>the findings highlight a novel, targeted and environmentally friendly approach for synthesizing AgNPs with promising anti-cancer potential while eliminating the use of toxic chemical agents.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 7","pages":"2190-2198"},"PeriodicalIF":0.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano-scaffolds for enhanced in-vitro and in-vivo anti-VEGFR drug delivery.","authors":"Arooj Khalid, Muhammad Yasir Ali, Romna Tul Janat, Mulazim Hussain Asim, Ijaz Ali, Daulat Haleem Khan, Umaira Rehman, Saima -, Asma Razzaq","doi":"10.36721/PJPS.2026.39.7.183.1","DOIUrl":"10.36721/PJPS.2026.39.7.183.1","url":null,"abstract":"<p><strong>Background: </strong>Sorafenib (SB) is a receptor tyrosine kinase inhibitor, currently marketed as an oral dosage form. However, due to severe irritation of the gastrointestinal tract, the drug is facing decreased acceptability as a therapeutic agent.</p><p><strong>Objectives: </strong>This study aimed to develop nano-scaffolds to increase the drug loading capacity and decrease the adverse drug reactions of SB.</p><p><strong>Method: </strong>Polymers used for the preparation of nano-scaffolds were polylactic co-glycolic acid (PLGA), ethyl cellulose (EC) and polyvinyl alcohol which was used as a surfactant. A range of different formulations was designed using 12.5 mg and 25 mg of EC, while the concentration of the PLGA was kept constant throughout the study. All formulations with or without the drug were characterized for size by dynamic light scattering (DLS), scanning electron microscopy, differential scanning calorimetry, hemolysis assay, cell viability assay, apoptotic assay and in-vivo evaluation.</p><p><strong>Results: </strong>DLS results showed the minimum nano-scaffold size of 252.8 ± 12 nm, which was increased by increasing the concentration of polymer and drug. The physicochemical assessment showed the presence of minor interactions between the polymeric system and SB. The cell viability assay showed the minimum cell viability at 50.66 ± 0.13 % at a maximum concentration of SB-loaded formulations, whereas the presence of apoptotic bodies confirmed these results.</p><p><strong>Conclusion: </strong>The in-vitro and in-vivo evaluation showed the safety profile of the polymeric PLGA/EC in the absence of drug content. Therefore, the fabricated system may be used as a carrier system for SB and can further be included in tumor model studies.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 7","pages":"1926-1938"},"PeriodicalIF":0.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin nanoparticles combined with narlumosbart regulate wingless-type MMTV integration site (wnt)/β-catenin signaling pathway in osteoblast-like cells.","authors":"Heng Zhang, Yonggang Zhao","doi":"10.36721/PJPS.2026.39.7.196.1","DOIUrl":"10.36721/PJPS.2026.39.7.196.1","url":null,"abstract":"<p><strong>Background: </strong>Narlumosbart is a key agent for modulating bone cell function. Given the potential of curcumin nanoparticles to inhibit cell growth when applied alone.</p><p><strong>Objectives: </strong>This study aims to investigate the role of their combination with narlumosbart in bone trauma repair and cell cycle regulation.</p><p><strong>Methods: </strong>Curcumin nanoparticles were fabricated and applied in combination with narlumosbart to treat MC3T3-E1 cells. The effects of this combination on osteoblast differentiation and proliferation were then assessed through immunofluorescence, protein expression analysis and ALP activity assays.</p><p><strong>Results: </strong>The combined use of curcumin nanoparticles and narlumosbart at 4 µM significantly enhanced inhibitory activity, indicating a synergistic therapeutic effect. Furthermore, immunohistochemistry revealed a marked increase in β-catenin expression and activation of the Wnt/β-catenin signaling pathway in the combination group. In contrast, while ALP staining confirmed elevated ALP activity, immunofluorescence detection showed no significant change in cell proliferation.</p><p><strong>Conclusion: </strong>Loaded within narlumosbart, curcumin nanoparticles can precisely modulate the Wnt/β-catenin pathway. This process specifically induces osteogenic differentiation without impacting proliferation, thereby directing cellular processes towards bone formation.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 7","pages":"2082-2088"},"PeriodicalIF":0.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of nifuratel-based therapy combined with vaginal lactobacillus probiotics on microecological restoration in pregnant women with abnormal vaginal flora: A retrospective cohort study.","authors":"Ya Luo, Hong Xu, Xiaohong Ye","doi":"10.36721/PJPS.2026.39.7.REG.189.1","DOIUrl":"10.36721/PJPS.2026.39.7.REG.189.1","url":null,"abstract":"<p><strong>Background: </strong>Imbalances in the vaginal flora during pregnancy elevate risks for adverse outcomes. While nifuratel targets pathogens, probiotics restore acidity, and robust cohort evidence supporting their combined safety and efficacy in restoring the microbiome remains limited.</p><p><strong>Objectives: </strong>This retrospective cohort study assessed nifuratel-nystatin therapy plus Lactobacillus probiotics for restoring vaginal flora in pregnancy.</p><p><strong>Methods: </strong>Employing a retrospective cohort design, this study enrolled pregnant women diagnosed with vaginal microecological abnormalities between March 2023 and 2024. Participants were allocated via 1:1 propensity score matching (PSM) into two groups (n=58 each): a combination group receiving nifuratel-nystatin therapy combined with vaginal Lactobacillus probiotics and a monotherapy group receiving nifuratel-nystatin alone. All received a 7-day treatment. The primary endpoint was clinical effectiveness assessed one week post-treatment. Secondary outcomes included vaginal pH, Lactobacillus and bacterial diversity normalization rates, recurrence, adverse pregnancy outcomes and drug-related adverse events, monitored until delivery. Multivariate logistic regression identified independent predictors of treatment efficacy.</p><p><strong>Results: </strong>After PSM, baseline characteristics were balanced (P>0.05). The comparative analysis indicated a superior overall efficacy for the combination therapy (93.1%) over monotherapy (77.6%), with statistical significance (P<0.01) Both groups exhibited reduced vaginal pH and increased rates of normalized Lactobacillus and bacterial diversity, with greater improvements observed in the combination group (P<0.01). The recurrence rate was significantly lower in the combination group (8.6% vs. 22.4%; P<0.05), as was the total incidence of adverse pregnancy outcomes (6.9% vs. 20.7%; P<0.01). No significant difference in adverse drug reactions was found. Multivariate analysis identified combination therapy as an independent protective factor for clinical efficacy (aOR=4.25, 95% CI: 1.42-12.71, P<0.05).</p><p><strong>Conclusions: </strong>In pregnant women with vaginal dysbiosis, combining nifuratel-nystatin with Lactobacillus probiotics safely enhances clinical efficacy, normalizes pH and flora and reduces adverse pregnancy outcomes.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 7","pages":"1993-2002"},"PeriodicalIF":0.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined effect of Withania somnifera and Syzygium cumini on hyperlipidemic patients.","authors":"Khizra Zubair, Faiqa Zafar, Summaya Saif, Uzma Khaliq, Hamna Syed, Amna Sarfraz, Shah Rukh Sultan, Muhammad Imran Hussain, Tanzeela Nisar","doi":"10.36721/PJPS.2026.39.7.200.1","DOIUrl":"10.36721/PJPS.2026.39.7.200.1","url":null,"abstract":"<p><strong>Background: </strong>Plants have long been used as natural remedies for various diseases. Withania somnifera and Syzygium cumini are known for their potential therapeutic effects, particularly in managing lipid disorders.</p><p><strong>Objectives: </strong>To evaluate the synergistic effects of Withania somnifera and Syzygium cumini on lipid profile in hyperlipidemic patients.</p><p><strong>Methods: </strong>This study included 60 patients, equally divided into four groups. Pre- and post-treatment assessments were conducted over 3 months. Group A (control) received Atorvastatin 10 mg HS; Group B received Withania somnifera (500 mg BD); Group C received Syzygium cumini (500 mg BD); and Group D received a combination of both (1000 mg QD). Data were analyzed using SPSS version 21 through paired sample t-test.</p><p><strong>Results: </strong>Withania somnifera showed significant improvement in low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL). Syzygium cumini significantly reduced cholesterol, triglycerides and systolic blood pressure. The combination therapy demonstrated the most pronounced effects, significantly reducing LDL, VLDL, cholesterol and triglycerides, while also improving high-density lipoproteins (HDL), without adverse effects.</p><p><strong>Conclusion: </strong>The combination of Withania somnifera and Syzygium cumini may be an effective and safe approach for managing hyperlipidaemia due to its beneficial impact on lipid profile.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 7","pages":"2120-2126"},"PeriodicalIF":0.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and biological evaluation of thiophene based oxadiazole derivatives as promising anticancer agents against liver cancer.","authors":"Zainib Razzaq, Samreen Gul Khan, Kiran Aftab, Fozia Anjum","doi":"10.36721/PJPS.2026.39.7.182.1","DOIUrl":"10.36721/PJPS.2026.39.7.182.1","url":null,"abstract":"<p><strong>Background: </strong>Liver cancer is a leading cause of cancer-related mortality worldwide. Clinical use of the first-line drug sorafenib is limited due to drug resistance and severe adverse effects.</p><p><strong>Objectives: </strong>The current study aimed to synthesize a series of N-arylated thiophene-based 1,3,4-oxadiazole derivatives containing a carbamothioate moiety (7a-7d) as potential anticancer agents with improved efficacy and safety profiles.</p><p><strong>Methods: </strong>Derivatives were synthesized via coupling of thiophene-based 1,3,4-oxadiazole (compound 1) with various electrophiles, yielding 62-86%. The structures of all derivatives were established based on FT-IR, ¹H NMR, ¹³C NMR, and EI-MS. The in-vitro anticancer effect of all derivatives was assessed using the MTT assay against the HepG2 cancer cell line and their hemolytic safety was assessed on human red blood cells.</p><p><strong>Results: </strong>All derivatives exhibited cytotoxicity with minimal hemolytic effects. Derivative 7b (2,6-dimethyl) exhibited excellent activity by reducing cell viability of 33.96 ± 2.47% at 100 μg/mL and minimal hemolysis (1.20 ± 0.01%) with a high selectivity index (SI) of 28.3, similar to sorafenib (34.32 ± 1.91%, SI = 27.45). Derivatives 7a (phenyl) and 7d (ethyl) showed moderate activity and 7c (fluoro) was the least potent.</p><p><strong>Conclusion: </strong>Thiophene-based oxadiazole-coupled carbamothioate derivatives, particularly 7b, demonstrate enhanced anticancer efficacy and safety compared to sorafenib, representing promising candidates for targeted liver cancer therapy.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"39 7","pages":"1917-1925"},"PeriodicalIF":0.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}