Archiv der Pharmazie最新文献

Discover the Power of Lithospermic Acid as Human Carbonic Anhydrase VA and Pancreatic Lipase Inhibitor Through In Silico and In Vitro Studies 通过硅学和体外研究发现石碳酸作为人体碳酸酐酶 VA 和胰脂肪酶抑制剂的威力

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-21 DOI: 10.1002/ardp.202500046

Emanuele Liborio Citriniti, Roberta Rocca, Giosuè Costa, Claudia Sciacca, Nunzio Cardullo, Vera Muccilli, Anastasia Karioti, Fabrizio Carta, Claudiu T. Supuran, Stefano Alcaro, Francesco Ortuso

{"title":"Discover the Power of Lithospermic Acid as Human Carbonic Anhydrase VA and Pancreatic Lipase Inhibitor Through In Silico and In Vitro Studies","authors":"Emanuele Liborio Citriniti, Roberta Rocca, Giosuè Costa, Claudia Sciacca, Nunzio Cardullo, Vera Muccilli, Anastasia Karioti, Fabrizio Carta, Claudiu T. Supuran, Stefano Alcaro, Francesco Ortuso","doi":"10.1002/ardp.202500046","DOIUrl":"https://doi.org/10.1002/ardp.202500046","url":null,"abstract":"Obesity remains a significant global health concern, with limited pharmacological options that balance efficacy and safety. In this study, we identified lithospermic acid (LTS0059529) from Salvia miltiorrhiza as a potential dual inhibitor of pancreatic lipase (PL) and human carbonic anhydrase VA (hCA VA), two key enzymes in lipid metabolism. Using molecular docking and dynamics simulations, we observed that lithospermic acid interacts with Zn²⁺ in hCA VA via its benzofuran carboxylate moiety and forms stable complexes with PL through hydrogen bonding with ASP 205 and π–stacking interactions with PHE 77 and PHE 215. Experimental validation confirmed its inhibitory activity, with Ki values of 33.1 ± 1.6 μM for PL and 0.69 ± 0.01 μM for hCA VA. While its inhibition of hCA VA is not isoform-specific, lithospermic acid demonstrates significant potential as a dual inhibitor, targeting complementary pathways in obesity management. This study is the first to explore its dual action on PL and hCA VA, highlighting a promising strategy for future antiobesity therapies. Further research will focus on optimizing selectivity and potency to develop safer and more effective treatments.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202500046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852663","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}

引用次数: 0

Advancements in Targeted Therapies for Colorectal Cancer: Innovative Drug Formulation and Delivery Strategies 结直肠癌靶向治疗的进展：创新药物配方和给药策略

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-21 DOI: 10.1002/ardp.202400969

Ali Ahmadizad Firouzjaei, Samira Mohammadi-Yeganeh

{"title":"Advancements in Targeted Therapies for Colorectal Cancer: Innovative Drug Formulation and Delivery Strategies","authors":"Ali Ahmadizad Firouzjaei, Samira Mohammadi-Yeganeh","doi":"10.1002/ardp.202400969","DOIUrl":"https://doi.org/10.1002/ardp.202400969","url":null,"abstract":"<div>\u0000 \u0000 Colorectal cancer (CRC) is a leading cause of cancer-related mortality globally, with increasing incidence presenting significant treatment challenges. Traditional nontargeted therapies often result in high toxicity and limited efficacy, underscoring the need for improved treatment modalities. This review highlights recent advancements in drug delivery systems to enhance therapeutic outcomes for CRC. We examine innovative strategies, including computer-assisted pharmaceutical formulation, sustained-release matrices, and prodrugs, as well as targeted delivery mechanisms such as exosomes, liposomes, hydrogels, antibody-drug conjugates, and stimuli-responsive systems. These methodologies offer improved drug biodistribution, enhanced targeting of cancer cells, and reduced off-target effects, promising better clinical outcomes. Additionally, we discuss the development of novel formulations designed to optimize the delivery of therapeutic agents in advanced CRC. Ongoing clinical trials investigating these innovative systems signify a shift toward more effective patient treatment options. While challenges remain in the clinical application of these targeted therapies, continued research offers promising avenues for improving patient outcomes in CRC. This study aims to inform future strategies for managing this aggressive disease, ultimately enhancing survival rates and quality of life for affected individuals.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis, Antituberculosis Evaluation and Structure–Activity Relationships of New SQ109 Analogs 新型SQ109类似物的合成、抗结核评价及构效关系

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-16 DOI: 10.1002/ardp.202400665

Dijovani Batista dos Reis, Emily Pacelli Moreira Linhares, Gabriel dos Santos e Silva, Frederico Henrique do Carmo Ferreira, Luiz Antônio Sodré Costa, Eloah Pereira Ávila, Mauro Vieira de Almeida, Marcus Vinícius Nora de Souza, Maria Cristina da Silva Lourenço, Mauricio Frota Saraiva

{"title":"Synthesis, Antituberculosis Evaluation and Structure–Activity Relationships of New SQ109 Analogs","authors":"Dijovani Batista dos Reis, Emily Pacelli Moreira Linhares, Gabriel dos Santos e Silva, Frederico Henrique do Carmo Ferreira, Luiz Antônio Sodré Costa, Eloah Pereira Ávila, Mauro Vieira de Almeida, Marcus Vinícius Nora de Souza, Maria Cristina da Silva Lourenço, Mauricio Frota Saraiva","doi":"10.1002/ardp.202400665","DOIUrl":"https://doi.org/10.1002/ardp.202400665","url":null,"abstract":"<div>\u0000 \u0000 Tuberculosis (TB) is a bacterial disease that poses significant challenges in its treatment. It requires prolonged use of high doses of medication, which can lead to various side effects. These side effects often contribute to low patient adherence to treatment, thereby increasing the risk of developing drug-resistant strains. The SQ109 is a second-generation agent developed from ethambutol that has been emerging as a promising TB agent. The functionalization of its skeleton appears as a strategy to improve the physicochemical and biological properties. Hence, we report the synthesis of functionalized SQ109 scaffolds, the in vitro evaluation against Mycobacterium tuberculosis H37Rv strains, molecular docking simulations, and molecular dynamics of the interactions with the target membrane protein.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification and Characterization of Interaction Product Impurities and Degradation Products of Atorvastatin Hot Melt Extrusion Formulation Using LC-HRMS/MS and ATR-IR 利用LC-HRMS/MS和ATR-IR对阿托伐他汀热熔挤压配方中相互作用产物杂质和降解产物进行鉴定和表征

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-14 DOI: 10.1002/ardp.202400955

Abhinav Mittal, Gauri Aras, V. K. Yuvaraaj, Devendra Badgujar, Derajram Benival, Nitish Sharma

{"title":"Identification and Characterization of Interaction Product Impurities and Degradation Products of Atorvastatin Hot Melt Extrusion Formulation Using LC-HRMS/MS and ATR-IR","authors":"Abhinav Mittal, Gauri Aras, V. K. Yuvaraaj, Devendra Badgujar, Derajram Benival, Nitish Sharma","doi":"10.1002/ardp.202400955","DOIUrl":"https://doi.org/10.1002/ardp.202400955","url":null,"abstract":"<div>\u0000 \u0000 Hot melt extrusion (HME) technology is widely used in pharmaceutical drug development to enhance the solubility and bioavailability of drugs. Atorvastatin (ATV) is a first-line statin for preventing cardiovascular disease, it has low oral bioavailability (14%), necessitating strategies to improve its bioavailability. This study involves identifying and characterizing interaction and degradation products formed during the HME process involving ATV and hydroxypropyl methylcellulose phthalate (HPMCP-55). It mainly focuses on identifying and characterizing unknown impurities and understanding their mechanisms. A simple, efficient, and mass spectrometry compatible high-performance liquid chromatography (HPLC) method was developed on a Welch XB C18 (4.6 × 150 mm, 3.5 μm) column using gradient elution of 10 mM ammonium acetate and acetonitrile as mobile phase. Further, attenuated total reflectance infrared spectrophotometry (ATR-IR) was also employed to investigate the interaction impurities formed between ATV and HPMCP-55 (imp-1,3) and degradation products (imp-2,4) formed during the extrusion process. LC-HRMS and ATR-IR analysis confirmed significant drug–polymer interactions during extrusion. Plausible impurity structures were elucidated via MS/MS fragmentation patterns and accurate mass. In silico toxicity prediction was performed using ProTox-II for all four impurities. The study underscores the importance of characterizing HME process impurities to understand drug stability, safety, and efficacy. This comprehensive approach facilitates thorough understanding of their potential interaction with drug candidates during the early phase of pharmaceutical development.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ternary Complex Modeling, Induced Fit Docking and Molecular Dynamics Simulations as a Successful Approach for the Design of VHL-Mediated PROTACs Targeting the Kinase FLT3 三元复合物建模、诱导拟合对接和分子动力学模拟作为vhl介导的靶向FLT3激酶的PROTACs设计的成功方法

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-14 DOI: 10.1002/ardp.202500102

Husam Nassar, Anne-Christin Sarnow, Ismail Celik, Mohamed Abdelsalam, Dina Robaa, Wolfgang Sippl

{"title":"Ternary Complex Modeling, Induced Fit Docking and Molecular Dynamics Simulations as a Successful Approach for the Design of VHL-Mediated PROTACs Targeting the Kinase FLT3","authors":"Husam Nassar, Anne-Christin Sarnow, Ismail Celik, Mohamed Abdelsalam, Dina Robaa, Wolfgang Sippl","doi":"10.1002/ardp.202500102","DOIUrl":"https://doi.org/10.1002/ardp.202500102","url":null,"abstract":"Proteolysis targeting chimeras (PROTACs) have proven to be a novel approach for the degradation of disease-causing proteins in drug discovery. One of the E3 ligases for which efficient PROTACs have been described is the Von Hippel-Lindau factor (VHL). However, the development of PROTACs has so far often relied on a minimum of computational tools, so that it is mostly based on a trial-and-error process. Therefore, there is a great need for resource- and time-efficient structure-based or computational approaches to streamline PROTAC design. In this study, we present a combined computational approach that integrates static ternary complex formation, induced-fit docking, and molecular dynamics (MD) simulations. Our methodology was tested using four experimentally derived ternary complex structures of VHL PROTACs, reported for BRD4, SMARCA2, FAK, and WEE1. In addition, we applied the validated approach to model a recently in-house developed FLT3-targeted PROTAC (MA49). The results show that static ternary models generated with a protein–protein docking method implemented in the software MOE have a high predictive power for reproducing the experimental 3D structures. The induced-fit docking of different active PROTACs to their respective models showed the reliability of this model for the development of new VHL-mediated degraders. In particular, the induced-fit docking was sensitive to structural changes in the PROTACs, as evidenced by the failed binding modes of the PROTAC negative controls. Furthermore, MD simulations confirmed the stability of the generated complexes and emphasized the importance of dynamic studies for understanding the relationship between PROTAC structure and function.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202500102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826961","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}

引用次数: 0

Unveiling the Therapeutic Potential of Dulaglutide in Mitigating Tacrolimus-Induced Nephrotoxicity Through Targeting the miR-22/HMGB-1/TLR4/MyD88/NF-κB Trajectory 通过靶向miR-22/HMGB-1/TLR4/MyD88/NF-κB轨迹，揭示杜拉鲁肽减轻他克莫司引起的肾毒性的治疗潜力

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-10 DOI: 10.1002/ardp.202500023

Rasha Abdelhady, Hany H. Arab, Rasha R. Fakhr Eldeen, Heba Nasr Shalaby, Dalia A. Nawwar, Mai Abdallah Elhemely, Rabab H. Sayed

{"title":"Unveiling the Therapeutic Potential of Dulaglutide in Mitigating Tacrolimus-Induced Nephrotoxicity Through Targeting the miR-22/HMGB-1/TLR4/MyD88/NF-κB Trajectory","authors":"Rasha Abdelhady, Hany H. Arab, Rasha R. Fakhr Eldeen, Heba Nasr Shalaby, Dalia A. Nawwar, Mai Abdallah Elhemely, Rabab H. Sayed","doi":"10.1002/ardp.202500023","DOIUrl":"https://doi.org/10.1002/ardp.202500023","url":null,"abstract":"Tacrolimus (Tac) is an immunosuppressive drug used to reduce the risk of allograft rejection; however, it can induce renal injury. High mobility group box 1 (HMGB-1) protein, which induces inflammation through the aberrant stimulation of the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response protein (MyD88)/nuclear factor kappa B (NF-κB) trajectory, could represent a molecular target for alleviating Tac-induced renal damage. The present study aimed to investigate the potential protective role of the GLP-1 agonist, dulaglutide (Dula), against Tac-induced nephrotoxicity in rats. Rats were administered Tac (5 mg/kg/day) and vehicle or Dula (0.2 mg/kg once a week) for 14 days. Treatment with Dula reduced serum creatinine plus blood urea nitrogen and attenuated Tac-induced renal histopathological changes. Dula treatment also hampered renal inflammation and restored redox homeostasis, as indicated by remarkably reduced tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and NADPH oxidase 1 levels alongside marked replenishment in reduced glutathione (GSH) content. These effects were mediated through the upregulation of miR-22 expression and the consequent inhibition of the HMGB-1/TLR4/MyD88/NF-κB trajectory. Collectively, Dula has been demonstrated to protect rats against Tac-induced nephrotoxicity by reducing inflammation, restoring redox homeostasis, and modulation of the miR-22/HMGB-1/TLR4/MyD88/NF-κB trajectory. Dula may be beneficial clinically in preventing Tac-induced renal injury.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202500023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809378","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}

引用次数: 0

WELPSA: A Green Catalyst Mediated Microwave Assisted Efficient Synthesis of Novel 5-Aminopyrazole-4-Carbonitrile Derivatives as Anticancer Agents (MCF-7, A-549) and In Silico Studies 绿色催化剂介导的微波辅助高效合成新型抗癌药物5-氨基吡唑-4-碳腈衍生物（MCF-7, A-549）及硅研究

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-08 DOI: 10.1002/ardp.202500055

Aravind R. Nesaragi, Vinuta Kamat, Sharanappa Chapi, Halligudra Guddappa, Sharanakumar T. M., Ala Chandu, Nabil Al-Zaqri, Ramasubba Reddy Palem, Sankaranarayanan Murugesan, Vijay M. Kumbar

{"title":"WELPSA: A Green Catalyst Mediated Microwave Assisted Efficient Synthesis of Novel 5-Aminopyrazole-4-Carbonitrile Derivatives as Anticancer Agents (MCF-7, A-549) and In Silico Studies","authors":"Aravind R. Nesaragi, Vinuta Kamat, Sharanappa Chapi, Halligudra Guddappa, Sharanakumar T. M., Ala Chandu, Nabil Al-Zaqri, Ramasubba Reddy Palem, Sankaranarayanan Murugesan, Vijay M. Kumbar","doi":"10.1002/ardp.202500055","DOIUrl":"https://doi.org/10.1002/ardp.202500055","url":null,"abstract":"<div>\u0000 \u0000 Malononitrile, modified hydrazine, and quinoline aldehyde were combined in a one-pot reaction under microwave irradiation to create the medicinally significant family of heterocyclic scaffolds, quinoline, coumarin, thiazole, and pyrazole 4-carbonitrile derivatives with the help of green solvent as water. WELPSA (water extract of lemon peel-soaked ash) is used to speed up the reaction in a solvent-free environment, according to more environmentally friendly reaction protocols. This methodology offers several advantages like short reaction duration, green solvent synthesis, high yield, no need for chromatographic techniques, catalyst recyclability of up to five cycles, and so on. Synthesized derivatives were evaluated for anticancer potential against lung (A549) and breast cancer cell lines. Among the tested compounds, 4i and 4j exhibited remarkable anticancer activities. Further investigations using Annexin V staining and flow cytometry revealed that both compounds effectively induced apoptosis in A549 cancer cells. Compound 4i was subjected to molecular docking and dynamic studies to understand the molecular basis of their activity, which demonstrated a strong interaction with the target protein 1m17, providing insights into its mechanism of action. These findings highlight the potential of compounds 4i and 4j as promising candidates for anticancer drug development.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Structural Insight Into Two Important ErbB Receptors (EGFR and HER2) and Their Relevance to Non-Small Cell Lung Cancer 两种重要ErbB受体（EGFR和HER2）的结构分析及其与非小细胞肺癌的相关性

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-07 DOI: 10.1002/ardp.202400992

Edanur Topalan, Ahmet Büyükgüngör, Melih Çiğdem, Sinan Güra, Belgin Sever, Masami Otsuka, Mikako Fujita, Hasan Demirci, Halilibrahim Ciftci

{"title":"A Structural Insight Into Two Important ErbB Receptors (EGFR and HER2) and Their Relevance to Non-Small Cell Lung Cancer","authors":"Edanur Topalan, Ahmet Büyükgüngör, Melih Çiğdem, Sinan Güra, Belgin Sever, Masami Otsuka, Mikako Fujita, Hasan Demirci, Halilibrahim Ciftci","doi":"10.1002/ardp.202400992","DOIUrl":"https://doi.org/10.1002/ardp.202400992","url":null,"abstract":"The epidermal growth factor receptor (EGFR) family, comprising receptor tyrosine kinases (RTK) such as EGFR and HER2, plays a critical role in various signaling pathways related to cell proliferation, differentiation, and growth. EGFR overactivation due to aberrant signaling can lead to various cancers, including non-small cell lung cancer (NSCLC). To develop treatment for EGFR-related NSCLC, several tyrosine kinase inhibitors (TKIs) were designed: gefitinib, erlotinib, as first-generation; neratinib, dacomitinib as second-generation; osimertinib, lazertinib as third-generation, as examples. However, due to the acquired resistance by the mutations such as EGFRT790M and EGFRC797S together with the exon 20 insertion mutations, these drugs do not provide promising results for NSCLC patients. The development of fourth-generation inhibitors like EAI045 and further innovative drugs to overcome this resistance problem is a must to cure EGFR-related NSCLC. Among these, pyrazoline-thiazole scaffolds are found effective as EGFR-HER2 inhibitors against NSCLC, making them promising drug candidates. Although structures obtained so far for the EGFR family provide meaningful insights into the mechanisms, the quality and the quantity of the EGFR family structures are insufficient to elucidate the complete structures and functions to overcome NSCLC. This review evaluates the structures of EGFR-HER2 and investigates their relation to NSCLC.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202400992","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793505","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}

引用次数: 0

Development of Potent Type V MAPK Inhibitors: Design, Synthesis, and Biological Evaluation of Benzothiazole Derivatives Targeting p38α MAPK in Breast Cancer Cells 有效的V型MAPK抑制剂的开发：乳腺癌细胞中靶向p38α MAPK的苯并噻唑衍生物的设计、合成和生物学评价

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-07 DOI: 10.1002/ardp.202500011

Bayan Zoatier, K. Gizem Yildiztekin, M. Abdullah Alagoz, Ceylan Hepokur, Serdar Burmaoglu, Oztekin Algul

{"title":"Development of Potent Type V MAPK Inhibitors: Design, Synthesis, and Biological Evaluation of Benzothiazole Derivatives Targeting p38α MAPK in Breast Cancer Cells","authors":"Bayan Zoatier, K. Gizem Yildiztekin, M. Abdullah Alagoz, Ceylan Hepokur, Serdar Burmaoglu, Oztekin Algul","doi":"10.1002/ardp.202500011","DOIUrl":"https://doi.org/10.1002/ardp.202500011","url":null,"abstract":"Type V MAPK inhibitors are distinguished by their capacity to target both the ATP binding site and a specific allosteric site on the enzyme. The present work utilized in silico analysis with Maestro 13.8.135 (Schrodinger) software in conjunction with experimental investigations to enhance the antiproliferative efficacy and forecast the likely mechanism of action of benzothiazole derivatives. Approximately 28 compounds were developed, produced, and assessed for their antiproliferative properties against two breast cancer cell lines: ER+ (MCF7) and ER- (MDA-MB-231), in addition to one normal mouse fibroblast cell line (L929). Their antiproliferative activities were evaluated via the MTT test, with doxorubicin and cisplatin serving as reference drugs for comparison. Consequently, the compounds with the greatest activity against the MCF7 cell line were chosen, and their inhibitory effects on the p38α MAPK enzyme were examined. The molecular docking studies of compounds 15 and 19 demonstrated significant binding affinities for p38α MAPK. Molecular dynamics simulations conducted over 100 ns revealed that compounds 15 and 19 exhibit stability inside both the ATP-binding domain and the lipid domain of p38α MAPK. The research focused on creating effective Type V MAPK inhibitors demonstrate that compounds 15 and 19 possess considerable ability to inhibit p38α MAPK, hence establishing them as promising anticancer agents.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202500011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793509","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}

引用次数: 0

Advances in the Development of Ferroptosis-Inducing Agents for Cancer Treatment 肿瘤诱导铁中毒剂的研究进展

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-03 DOI: 10.1002/ardp.202500010

Li Zhang, Yulong Li, Yufeng Qian, Ruliang Xie, Wei Peng, Wen Zhou

{"title":"Advances in the Development of Ferroptosis-Inducing Agents for Cancer Treatment","authors":"Li Zhang, Yulong Li, Yufeng Qian, Ruliang Xie, Wei Peng, Wen Zhou","doi":"10.1002/ardp.202500010","DOIUrl":"https://doi.org/10.1002/ardp.202500010","url":null,"abstract":"<div>\u0000 \u0000 Cancer is the main leading cause of death worldwide and poses a great threat to human life and health. Although pharmacological treatment with chemotherapy and immunotherapy is the main therapeutic strategy for cancer patients, there are still many shortcomings during the treatment such as incomplete killing of cancer cells and development of drug resistance. Emerging evidence indicates the promise of inducing ferroptosis for cancer treatment, particularly for eliminating aggressive malignancies that are resistant to conventional therapies. This review covers recent advances in important regulatory targets in the ferroptosis metabolic pathway and ferroptosis inducers (focusing mainly on the last 3 years) to delineate their design, mechanisms of action, and anticancer applications. To date, many compounds, including inhibitors, degraders, and active molecules from traditional Chinese medicine, have been demonstrated to have ferroptosis-inducing activity by targeting the different biomolecules in the ferroptosis pathway. However, strictly defined ferroptosis inducers have not yet been approved for clinical use; therefore, the discovery of new highly active, less toxic, and selective compounds remains the goal of further research in the coming years.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0