Drug Development Research最新文献

{"title":"Dihydroartemisinin Attenuates Radiation-Induced Lung Injury by Inhibiting the cGAS/STING/NF-κB Signaling Pathway","authors":"Cailan Wang,&nbsp;Xinyi Lin,&nbsp;Shichun Guan,&nbsp;Qiaoyuan Wu,&nbsp;Shixiong Liang","doi":"10.1002/ddr.70090","DOIUrl":"https://doi.org/10.1002/ddr.70090","url":null,"abstract":"<p>Dihydroartemisinin (DHA) is a derivative of artemisinin, which affects inflammation, oxidative stress, and immune regulation. However, the mechanism underlying its effects remains largely unknown. This study aims to explore the mechanism by which DHA affects radiation-induced lung injury (RILI), providing new insights for lung radiotherapy. To elucidate its mechanism of action, C57BL/6 J mice were irradiated with 15 Gy whole chest. RILI was evaluated by qRT-PCR, ELISA, histology, Western blot analysis, immunohistochemistry, and RILI signaling cascade studies. In addition, small interfering RNAs were employed to knockdown cGAS proteins in the cGAS-STING signaling pathway in the human bronchial epithelium cell line (BEAS-2B). Both In Vivo and Vitro experiments were conducted to investigate the specific mechanism by which DHA alleviated RILI. We observed the activation of the cGAS-STING pathway, along with the phosphorylation of the downstream target NF-κB and an increase in inflammatory factor levels in the mouse model following radiation exposure. In the cell model, irradiation also triggered the activation of the cGAS-STING signaling pathway and its downstream targets, leading to elevated levels of inflammatory factors. Notably, knocking down the cGAS using small interfering RNA in the BEAS-2B cells significantly alleviated RILI in the cell model. Our study elucidated the mechanism of DHA reducing RILI through the cGAS/STING/NF-κB signaling pathway, and revealed that the GAS/STING/NF-κB axis may be a potential therapeutic target for RILI.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Treatment: The Role of Pharmacology, Genomics, and AI in Improving Patient Outcomes","authors":"Fazil Ahmad","doi":"10.1002/ddr.70093","DOIUrl":"https://doi.org/10.1002/ddr.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>Recent advances in pharmacology are revolutionizing drug discovery and treatment strategies through personalized medicine, pharmacogenomics, and artificial intelligence (AI). The objective of the present study is to review the role of personalized medicine, pharmacogenomics, and AI-based strategies in optimizing patient outcomes with improved drug efficacy and reduced side effects. A comprehensive review was performed to debate the utility of pharmacogenomics in the prediction of drug response, the role of AI in drug discovery, and the utility of personalized medicine in the clinic. This review highlights how drug discovery and treatment techniques are evolving with the aid of personalized medicine, pharmacogenomics, and AI. Personalized medicine makes the treatment fit the DNA pattern for higher efficacy and minimal side effects. Pharmacogenomics forecasts the action of a drug in terms of genetic difference. AI speeds up drug discovery to enhance the effectiveness and accuracy of finding and evaluating drug leads. Studies show that customized medicine charts therapy to an individual patient's individual genetic profile, resulting in better therapy. Pharmacogenomics facilitates precise drug selection by considering genetic variations, reducing adverse reactions. AI speeds up drug discovery by applying predictive modeling and data-driven evaluation to propel optimized drug development pathways. Together, these advances are enabling more efficient and safer treatment practices across medical disciplines. The combination of pharmacology, genomics, and AI is revolutionizing contemporary healthcare through the personalization of treatments, improved drug safety, and therapeutic outcomes. The future of research should be on optimizing these techniques and overcoming ethical and regulatory issues to facilitate broader clinical implementation.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875648","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":"miR-338-3p Targets SIRT6 to Inhibit Liver Cancer Malignancy and Paclitaxel Resistance","authors":"Yiyuan Huang,&nbsp;Sunhui Huang,&nbsp;Quan Li,&nbsp;Hongchang Zhang,&nbsp;Wei Xiao,&nbsp;Yunhui Chen","doi":"10.1002/ddr.70089","DOIUrl":"https://doi.org/10.1002/ddr.70089","url":null,"abstract":"<div>\u0000 \u0000 <p>For patients with liver cancer, a widespread and lethal tumor on a global scale, chemotherapy and immunotherapy are often the top choices. Paclitaxel, a widely administered chemotherapy drug, faces the dual issues of poor tumor response rates and the rapid onset of chemoresistance. This study delves into the functions of SIRT6 and miR-338-3p in malignancy and paclitaxel resistance of liver cancer cells. Bioinformatics and qRT-PCR were engaged to predict and examine expression profiles of SIRT6 and miR-338-3p in liver cancer tissues and cell lines. A paclitaxel-resistant cell line (MHCC97-PTX) was established for dissecting cellular responses to drug treatment. CCK-8 and colony formation tests measured cell vitality and proliferation, respectively. Flow cytometry assessed apoptotic cell death, and the paclitaxel IC₅₀ values were derived for each group. We utilized online tools to predict miR-338-3p as an upstream regulator of SIRT6, and a dual-luciferase reporter assay verified their direct interaction. SIRT6 is abundantly expressed in liver cancer tissues and cells. SIRT6 knockdown decreased cell vitality and proliferation while promoting apoptosis and paclitaxel sensitivity. miR-338-3p, an upstream regulator of SIRT6 in liver cancer cells, binds to SIRT6 and downregulates its expression, modulating cell malignancy and drug resistance. The duo of miR-338-3p and SIRT6 can drive the aggressiveness and chemoresistance of liver cancer, emerging as hopeful candidates for biomarkers and therapeutic targets.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856722","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":"FOXA1 Targets NEK2 to Mediate Cisplatin Resistance in Lung Adenocarcinoma Cells by Activating DNA Damage Repair","authors":"Junhong Yang,&nbsp;Guangcheng Yue,&nbsp;Zhiguo Fan,&nbsp;Ning Zhang,&nbsp;Shiwei Nie,&nbsp;Jing Li,&nbsp;Yuanyuan Ji","doi":"10.1002/ddr.70087","DOIUrl":"https://doi.org/10.1002/ddr.70087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Lung adenocarcinoma (LUAD) is one of the main causes of death in cancer patients, as its hidden course is difficult to uncover, resulting in many patients being diagnosed as advanced. Late-stage LUAD patients are prone to develop resistance to cisplatin. This study aims to explore the potential molecular regulatory mechanism of NEK2 on cisplatin resistance in LUAD cells. The expression levels of NEK2 and FOXA1 in LUAD tissues were analyzed based on bioinformatics methods. qRT-PCR analysis was carried out to measure the mRNA expression levels of NEK2 and FOXA1 in LUAD cells. CCK8 detected and calculated cell viability and IC₅₀ values for each group of cells. Gene set enrichment analysis (GSEA) analyzed signaling pathways enriched by the NEK2 gene in LUAD. Dual luciferase and CHIP experiments were conducted to verify the binding relationship between NEK2 and FOXA1. Comet assay was utilized to analyze the level of DNA damage in LUAD cells. Western blot (WB) measured the expression levels of DNA damage-related proteins (γ-H2AX, p-ATM). The experimental results showed that FOXA1 and NEK2 were highly expressed in LUAD tissues and cells. GSEA analysis showed that NEK2 was enriched in DNA damage-related pathways, and silencing NEK2 could reduce the vitality of LUAD cisplatin-resistant cells, lower the IC₅₀ value of cells to cisplatin, and increase their DNA damage levels. FOXA1 can target the promoter region that binds to NEK2, and it can activate NEK2 through transcription to promote DNA damage repair and cisplatin resistance in cisplatin-resistant LUAD cells. This study confirms that FOXA1 can target NEK2 to promote DNA damage repair and cisplatin resistance in LUAD cells, providing a new valuable therapeutic target for the treatment of LUAD and the control of chemotherapy drug resistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835921","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":"Diaryl Diimidazopyrimidine Derivatives as Potent Inhibitors of Influenza A Virus: Synthesis, Evaluation and Docking Studies","authors":"Abburi Naga Pranathi,&nbsp;Devendra Nagineni,&nbsp;Rakesh Kumar Bollikanda,&nbsp;Svetlana V. Belyaevskaya,&nbsp;Iana L. Esaulkova,&nbsp;Vladimir V. Zarubaev,&nbsp;Balasubramanian Sridhar,&nbsp;Manikanta Murahari,&nbsp;Srinivas Kantevari","doi":"10.1002/ddr.70088","DOIUrl":"https://doi.org/10.1002/ddr.70088","url":null,"abstract":"<div>\u0000 \u0000 <p>In this report, we present a new series of diaryl diimidazopyrimidine derivatives <b>3a-m,</b> that have been synthesized and assessed for their in vitro antiviral activity. The derivatives were prepared through a one-step reaction involving commercially available 2,4-diamino-6-chloropyrimidine and various phenacyl bromides <b>2a-m</b>, leading to the formation of the desired diaryl diimidazo- pyrimidines <b>3a-m</b> with good yields. <i>In vitro</i> evaluations against the <i>Influenza A</i> H1N1 strain identified compounds <b>3m</b> (SI = 73) and <b>3b</b> (SI = 23) as the most potent candidates. Additionally, antimicrobial screening indicated that compounds <b>3d</b> and <b>3j,</b> which contain methyl and methoxy substitutions, exhibited moderate activity against <i>Streptococcus mutans</i>, <i>Salmonella typhi</i>, and <i>Candida albicans</i>. Molecular Docking studies of the promising compounds <b>3b and 3m</b> demonstrated significant binding interactions with the M1 matrix protein (PDB ID: 5CQE) in comparison to M2 proton channel of <i>Influenza A</i> (PDB: 6US9), suggesting that these derivatives may be effectively targeting the M1 protein. Additionally, molecular dynamics (MD) simulations were conducted to evaluate the stability, dynamic behaviour, and binding affinity of the most potent compounds <b>3b</b> and <b>3m.</b> The in vitro antiviral studies, molecular docking and MD simulations data highlight the promising pharmacological potential of these analogues, paving the way for further structural optimization and development as potential antiviral agents.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827044","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":"Sirtuin 1 Is a Potential Target for the Treatment of Neurogenic Intermittent Claudication by Modulating Pyroptosis","authors":"Xuejian Dan,&nbsp;Hong Wu,&nbsp;Wei Liu,&nbsp;Xiao Hu,&nbsp;Wei Xu,&nbsp;Chen Li,&nbsp;Bin Ma","doi":"10.1002/ddr.70083","DOIUrl":"https://doi.org/10.1002/ddr.70083","url":null,"abstract":"<div>\u0000 \u0000 <p>Neurogenic intermittent claudication (NIC) pathogenesis associated with lumbar spinal stenosis (LSS) remains unclear. However, pyroptosis has been implicated in the pathogenesis of various central nervous system disorders. Therefore, the present study aimed to explore the potential role of pyroptosis in NIC progression. Additionally, the present study investigated the possible involvement of Sirtuin 1 (Sirt1), a protein recognized for its neuroprotective properties, in mitigating the progression of NIC by alleviating pyroptosis. In the current study, a rat model of NIC associated with LSS was successfully constructed by inserting a silicone strip into the vertebral plates. The Basso Beattie Bresnahan score was employed to assess the motor function of rats. Western blot analysis was performed to measure the levels of pyroptosis-related proteins in rat spinal cord tissue. Meanwhile, PC-12 cells were cultured with H₂O₂ to establish an in vitro model of oxidative stress, allowing to investigate the effects of Sirt1 on cell pyroptosis and oxidative stress in H₂O₂-treated cells. The current results showed that rats with NIC developed both motor and sensory dysfunction. Additionally, NIC surgery notably elevated NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), gasdermin D N-terminal (GSDMD-N), and IL-1β levels in the spinal cord tissues of rats, suggesting that pyroptosis is activated in the context of NIC. Significantly, downregulation of Sirt1 exacerbated malondialdehyde and reactive oxygen species levels, and simultaneously reduced GSH levels in H₂O₂-stimulated PC-12 cells, suggesting that Sirt1 deficiency can aggravate oxidative stress. Meanwhile, downregulation of Sirt1 also led to increased levels of NLRP3, ASC, GSDMD-N, and cleaved caspase 1 in H₂O₂-stimulated PC-12 cells, suggesting that Sirt1 deficiency can further enhance the pyroptosis in these cells. Targeting pyroptosis signaling may yield new insights into the treatment of NIC. The mechanisms mediated by pyroptosis could offer valuable perspectives on the pathogenesis and management of this condition.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801285","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":"HIF–Prolyl Hydroxylase Inhibitor Desidustat Increases Pyruvate Kinase Activity and Reduces Oxidative Stress in Red Blood Cells, Causes Erythrocytosis in Thalassaemic Mice, and Reduces Sickling in Sickle Cell Patient's Blood","authors":"Vishal J. Patel,&nbsp;Amit A. Joharapurkar,&nbsp;Samadhan G. Kshirsagar,&nbsp;Maulik S. Patel,&nbsp;Hardikkumar H. Savsani,&nbsp;Milan H. Rakhasiya,&nbsp;Harshad S. Dodiya,&nbsp;Mukul R. Jain","doi":"10.1002/ddr.70086","DOIUrl":"https://doi.org/10.1002/ddr.70086","url":null,"abstract":"<div>\u0000 \u0000 <p>Sickle cell anemia and beta-thalassemia are the major hemoglobinopathies associated with anemia. Bone marrow transplants or blood transfusion are frequently employed as treatment for these diseases, and erythropoietin analogues are sometimes used to boost erythropoiesis to compensate the destruction of RBCs. RBCs of hemoglobinopathy patients have reduced pyruvate kinase activity and increased oxidative stress, which makes the RBCs prone to destruction and precipitate vaso-occlusive crises and pain. The objective of this study was to evaluate desidustat, a hypoxia inducible factor (HIF) stabilizer in beta thalassemic mice (B6.D2-Hbb^d3th/BrkJ) model, phenylhydrazine-induced acute hemolysis in C57 mice model, and sodium metabisulfite-induced sickling in sickle cell disease patient's blood. Desidustat treatment increased hemoglobin, RBCs, and hematocrit in both mice models. Desidustat treatment decreased iron overload, splenomegaly, and oxidative stress in phenylhydrazine-induced hemolytic anemia in mice. Desidustat treatment increased pyruvate kinase activity in RBCs of human, mice, and rats in a dose-dependent manner, and reduced sickling in SCD patients' RBCs. These data indicate that desidustat stimulates pyruvate kinase and attenuates oxidative stress in red blood cells, causes erythrocytosis in thalassemic mice, and reduces sickling in sickle cell patient's blood.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786792","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":"Imidazolidine-Based Aspartate Inhibitors for Candida Infections","authors":"B. Bindu,&nbsp;A. Manikandan,&nbsp;S. Jeevitha,&nbsp;Joe Jacob Kunju,&nbsp;S. Vijayalakshmi","doi":"10.1002/ddr.70074","DOIUrl":"https://doi.org/10.1002/ddr.70074","url":null,"abstract":"<div>\u0000 \u0000 <p>The fungal infection gradually poses a life threat to mankind, candidiasis caused by Candida sp. is one among them. We describe the aspartate protease inhibition potentials of 12 sulfonyl-containing imidazolidines (<b>5a-l</b>) anti-candidal agents. <i>Candida Albicans</i> secretes aspartic proteases (Saps), one of its most important virulent agents. These hydrolytic enzymes are critical for both fungal physiological processes and host-fungus interactions. Compounds <b>5a-l</b> were examined for their fungal aspartate protease inhibition apart from their anti-candida activity. These findings were equipped and validated in silico using molecular docking and in vitro enzyme inhibition assays. The study found that imidazolidine derivatives inhibited aspartic protease and exhibited anti-candida action. Conclusively, imidazolidines <b>5g, 5h,</b> and <b>5j</b> were perceived as the most potent anti-candida compounds and are presently being evaluated for their preclinical studies.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741694","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":"Novel 3-Substituted-2H-Chromene Scaffold Based Fluorinated Hydrophobic Fragment as In-Vitro Antiproliferative Agents and Apoptosis Inducers Targeting Both VEGFR-2/BRAFV600E and h-DHFR With Molecular Docking Simulation","authors":"Mohamed A. Salem,&nbsp;Moustafa S. Abusaif,&nbsp;Nirvana A. Gohar,&nbsp;Yousry A. Ammar,&nbsp;Ahmed Ragab","doi":"10.1002/ddr.70085","DOIUrl":"https://doi.org/10.1002/ddr.70085","url":null,"abstract":"<div>\u0000 \u0000 <p>Recently, there has been an increasing interest in the use of protein kinase inhibitors as a therapeutic strategy for the treatment of cancer. In this study, a new series of 2<i>H</i>-chromene derivatives (<b>2</b>-<b>5</b> and <b>6</b>-<b>8</b>) and 3<i>H</i>-benzo[<i>f</i>]chromene carbohydrazide derivative (<b>9</b>) were synthesized. The structure of the designed derivatives was characterized by IR, ¹H/¹³C NMR, and elemental analysis. Moreover, the cytotoxic activity of the newly synthesized chromenes was evaluated against breast cancer cell lines (MDA-MB-231 and MCF-7) and a cervical cancer cell line (HeLa). The results of these evaluations demonstrated promising activity, ranging from good to moderate. Additionally, the lung fibroblast cell line (WI-38), as a normal cell line, was also utilized to assess the active derivatives' selectivity. Among the compounds tested, chromene derivative <b>3</b> demonstrated the highest potency, exhibiting IC₅₀ values of 5.36 ± 0.50, 7.82 ± 0.60, and 9.28 ± 0.70 µM against the MDA-MB 231, MCF-7, and HeLa cell lines, respectively. The potential of chromone <b>3</b> as a multi-targeted anticancer agent was assessed by evaluating its activity against BRAF and VEGFR-2. Notably, the most promising chromene derivative <b>3</b> demonstrated significant VEGFR2 activity with an IC₅₀ value of 0.224 µM compared to sorafenib's 0.045 µM, while exhibiting inhibitory activity against BRAF with an IC₅₀ value of 1.695 µM relative to Vemurafenib's IC₅₀ value of 0.468 µM. In addition, compound <b>3</b> inhibits the DHFR enzyme with an IC₅₀ value of 2.217 ± 0.014 µM, compared to methotrexate (IC₅₀ = 0.4315 ± 0.019 µM). These results revealed that the compound has multifaceted mechanisms of action that may augment its therapeutic effectiveness. In addition, compound <b>3</b> causes overexpression of caspase-3 and Bax by 6.13 and 8.85-fold, respectively. It also downregulates the antiapoptotic Bcl-2 level by 0.4775-fold compared to the untreated MDA-MB 231 cells. Flow cytometry analysis of MDA-MB-231 cells indicates that compound 3 induces cell cycle arrest in the G0-G1 phase, with an observed percentage of 73.15%. The in-silico toxicity prediction was evaluated and demonstrated a good toxicity profile. Finally, molecular docking studies supported these findings by confirming strong binding affinities of the derivatives to VEGFR-2, BRAF, and DHFR.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717187","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":"Carboxymethyl Starch: A Contemporary Paradigm for Anti Cancer Drug Delivery","authors":"Rabab Fatima","doi":"10.1002/ddr.70082","DOIUrl":"https://doi.org/10.1002/ddr.70082","url":null,"abstract":"<div>\u0000 \u0000 <p>Carboxymethyl starch (CMS) represents a significant advancement in addressing the multifaceted challenges of anticancer drug delivery, including poor aqueous solubility, nonspecific biodistribution, and premature drug release. The strategic incorporation of carboxymethyl moiety (-CH₂COOH) onto the starch backbone confers a suite of physicochemical properties that markedly enhance its efficacy as a drug carrier. The carboxymethyl groups, with a pKa of approximately 4.5, exhibit pronounced pH-responsiveness, undergoing a transition from a predominantly deprotonated, hydrophilic state at physiological pH (7.4) to a more protonated form in the acidic tumor microenvironment (pH 6.5–6.8) facilitating targeted drug release at neoplastic site. The mucoadhesive attributes ascribable to carboxyl-mucin interactions, prolong gastrointestinal residence time for oral formulations, optimizing drug absorption. Furthermore, these functional groups serve as reactive sites for subsequent modifications, facilitating the development of multifunctional, targeted drug delivery systems with enhanced biocompatibility and minimized off-target effects. The versatility and biocompatibility of CMS position it as a promising platform for next-generation anticancer therapeutics, offering potential for significant advancements in oncological treatment modalities.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707577","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}