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Synergistic Induction of Apoptosis and Cell Cycle Arrest against Breast Cancer Cells by Combined Kaempferol and Paclitaxel. 山奈酚和紫杉醇联合应用对乳腺癌细胞凋亡和细胞周期阻滞的协同诱导作用。
IF 1.7
Drug Research Pub Date : 2025-07-14 DOI: 10.1055/a-2637-1672
Toofan Aghazadeh, Fatemeh Ramezani, Nuredin Bakhtiari, Isa Abdi Rad
{"title":"Synergistic Induction of Apoptosis and Cell Cycle Arrest against Breast Cancer Cells by Combined Kaempferol and Paclitaxel.","authors":"Toofan Aghazadeh, Fatemeh Ramezani, Nuredin Bakhtiari, Isa Abdi Rad","doi":"10.1055/a-2637-1672","DOIUrl":"https://doi.org/10.1055/a-2637-1672","url":null,"abstract":"<p><p>The study investigates the potential of combining Kaempferol (KAE) and Paclitaxel (PAC) to enhance anti-cancer effects and induce apoptosis in MDA-MB-468 triple-negative breast cancer cells and human normal foreskin fibroblast cells.For this porpose, the cells were treated with PAC, KAE, and their combination for 24, 48, and 72 hours. Cytotoxicity was assessed via MTT assay, and synergy was evaluated using Combination Index analysis. Apoptosis was quantified via Annexin V/PI staining and DAPI staining. Flow cytometry analyzed cell cycle arrest, while qPCR assessed apoptotic gene expression.The combination of KAE and PAC exhibited a synergistic anti-proliferative effect, significantly reducing MDA-MB-468 cell viability compared to monotherapies. Annexin V/PI staining revealed an increased apoptotic rate (73%) in co-treated cells, with enhanced chromatin condensation and nuclear fragmentation observed via DAPI staining. Flow cytometry indicated a marked increase in SubG1 phase cells, confirming apoptosis induction. Gene expression analysis demonstrated upregulation of pro-apoptotic BAD and downregulation of anti-apoptotic Bcl-2 and Mcl-1, highlighting the activation of apoptosis pathways.The combination of PAC and KAE enhances cytotoxicity, promotes apoptosis, and alters key apoptotic gene expressions in MDA-MB-468 cells while sparing normal fibroblast cells. These findings suggest a promising therapeutic strategy for triple-negative breast cancer.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Design and Optimization of Novel Pyrimidine-Morpholine Hybrids Through Computational Approaches for SRC Kinase Inhibitory Activity. 基于SRC激酶抑制活性计算方法的新型嘧啶-啉杂合体设计与优化。
IF 1.7
Drug Research Pub Date : 2025-07-01 Epub Date: 2025-04-17 DOI: 10.1055/a-2554-1119
Knolin K Thachil, V Soumya
{"title":"Design and Optimization of Novel Pyrimidine-Morpholine Hybrids Through Computational Approaches for SRC Kinase Inhibitory Activity.","authors":"Knolin K Thachil, V Soumya","doi":"10.1055/a-2554-1119","DOIUrl":"10.1055/a-2554-1119","url":null,"abstract":"<p><p>Src (non receptor tyrosine kinase) plays a role in multiple pathways leading to tumor survival, proliferation and metastasis. Inhibiting Src kinase would be a therapeutic benefit in Src dependent cancers. Most of the nitrogen containing heterocyclic moieties found to possess variety of biological activities. Combination of heterocyclic nucleus to active hybrids has proven to be a successful method of approach to augment biological activities. Hence a series of pyrimidine-morpholine hybrids were designed and its shape similarity studies calculated with the standard Dasatinib using Tanimoto coefficient. Designed molecules were docked with human tyrosine kinase (PDB ID: 2SRC) using AutoDock vina. Docked poses were ranked based on their binding affinities which are then compared with a reference. The studies revealed that docking of hybrid molecules with 2SRC showed promising interactions with affordable ADMET properties. The stability of highly docked complex was analyzed by molecular simulation studies and the results confirmed the docking outcomes thereby making it as a potential SRC kinase inhibitor. Hence these novel pyrimidine hybrids can be considered as lead molecules for developing novel druggable moieties for breast cancer research.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"209-217"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Real-world Pharmacovigilance Study Of FDA Adverse Event Reporting System (FAERS) Events For Gender Of Voriconazole Drugs. FDA不良事件报告系统(FAERS)对伏立康唑药物性别事件的现实药物警戒研究。
IF 1.7
Drug Research Pub Date : 2025-07-01 Epub Date: 2025-04-28 DOI: 10.1055/a-2575-1530
Qiong Xu, Hongxia Cheng, Xu Sun, Jing Zhao, Yingying Chen, Lingyu Ji, Yan Liang
{"title":"A Real-world Pharmacovigilance Study Of FDA Adverse Event Reporting System (FAERS) Events For Gender Of Voriconazole Drugs.","authors":"Qiong Xu, Hongxia Cheng, Xu Sun, Jing Zhao, Yingying Chen, Lingyu Ji, Yan Liang","doi":"10.1055/a-2575-1530","DOIUrl":"10.1055/a-2575-1530","url":null,"abstract":"<p><p>To detect the gender variations in adverse events (AEs) of voriconazole, promote personalised medicine.A normalized dataset from Q1 2004 to Q4 2022 from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) was analyses. The reporting odds ratio (ROR), proportional reporting ratio (PRR), and P value were used to examine data from the FAERS database to detect risk signals and quantify the presence and extent of gender variations in voriconazole adverse events.A total of 7670 cases (female/male (2785/4885)) of adverse reactions to voriconazole were analysed, and drug interaction (ROR 1.30 (1.10,1.54)), death and sudden death (ROR 1.31 (1.06,1.61)), actinic keratosis (ROR 1.98 (1.10,3.57)) were found to be significantly more frequent in male patients than in female patients.We found that gender was a determinant in voriconazole-related AEs using FAERS. Our results require future validation due to the inherent limits of this open data source, but they also identify potential contributing elements for a customised side effect profiling.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"218-224"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing Doxorubicin Sensitivity in Osteosarcoma Cancer Cells: Unveiling the Role of Resveratrol-Induced Oxidative DNA Damage. 增强阿霉素在骨肉瘤癌细胞中的敏感性:揭示白藜芦醇诱导的DNA氧化损伤的作用。
IF 1.7
Drug Research Pub Date : 2025-07-01 Epub Date: 2025-04-24 DOI: 10.1055/a-2567-9916
Mohammad Reza Bazavar, Hamed Helali, Linda Mohammadzadeh Boukani, Bahman Yousefi, Amir Valizadeh
{"title":"Enhancing Doxorubicin Sensitivity in Osteosarcoma Cancer Cells: Unveiling the Role of Resveratrol-Induced Oxidative DNA Damage.","authors":"Mohammad Reza Bazavar, Hamed Helali, Linda Mohammadzadeh Boukani, Bahman Yousefi, Amir Valizadeh","doi":"10.1055/a-2567-9916","DOIUrl":"10.1055/a-2567-9916","url":null,"abstract":"<p><p>Our current research aims to investigate how Resveratrol influences DOX-induced apoptosis in Saos-2 cells resulting from DNA damage.Saos-2 cells were cultured with DOX, and an MTT assay was conducted to evaluate cell viability. The expression levels of DNA damage markers were evaluated using qRT-PCR and western blotting methods. Apoptosis was also investigated by flow cytometry.In a dose-dependent way, DOX produced a profuse suppression of cell proliferation. This study investigates the effect of Resveratrol on DOX-induced apoptosis due to DNA damage in Saos-2 cells (<i>P</i><0.05). There was an increase in H2AX, ATR, ATM, Rad51, and p53 expression, possibly contributing to subsequent apoptosis. Furthermore, Resv enhanced the apoptosis caused by DOX in Saos-2 cells.The findings from the current research provide an understanding of how Resv plays a role in potentially treating osteosarcoma by enhancing DOX-induced apoptosis.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"202-208"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective Effects of Niclosamide Ethanolamine Against Testosterone-Induced Benign Prostatic Hyperplasia in Rats. 氯硝胺乙醇胺对睾酮诱导的大鼠良性前列腺增生的保护作用。
IF 1.7
Drug Research Pub Date : 2025-07-01 Epub Date: 2025-04-28 DOI: 10.1055/a-2576-4153
Ali Hussein Jasim, Ahmed Rahmah Abu-Raghif, Zeena Ayad Hussein
{"title":"Protective Effects of Niclosamide Ethanolamine Against Testosterone-Induced Benign Prostatic Hyperplasia in Rats.","authors":"Ali Hussein Jasim, Ahmed Rahmah Abu-Raghif, Zeena Ayad Hussein","doi":"10.1055/a-2576-4153","DOIUrl":"10.1055/a-2576-4153","url":null,"abstract":"<p><p>Benign prostatic hyperplasia is a common urological condition in aging men. The anthelmintic agent niclosamide ethanolamide exhibits a wide range of pharmacological activities. This study aimed to evaluate the protective effect of niclosamide ethanolamide in testosterone propionate-induced benign prostatic hyperplasia in rats along with elucidating the probable mechanism of action by investigating the influence on PPAR-γ and Wnt/β-catenin. 40 male Wistar rats were divided randomly into 4 groups. The healthy (control) group, received daily oral and subcutaneous administration of the vehicle. The Induced (TP) group, received only a daily dose of testosterone propionate 3 mg/kg, SC for 28 days. The treated groups (TP+FIN) and (TP+NE), received a concomitant administration of a daily dose of testosterone propionate along with finasteride 5 mg/kg/day and niclosamide ethanolamide 50 mg/kg/day respectively through oral gavage. Animals were euthanized on day 30 of the experiment and prostate tissue samples were collected to evaluate prostate index, prostate hyperplastic markers by ELISA, and gene expression by RT-qPCR. Results revealed that niclosamide ethanolamide significantly reduced prostate index compared to the induced (TP) group (P<0.0001). The agent nearly normalized BPH markers including 5α-reductase type-2 enzyme, dihydrotestosterone, and PCNA compared to the induced (TP) group (P<0.0001). The agent reduced the tissue level of β-catenin while elevating PPAR-γ to control levels (P<0.05). The current study revealed that NE can help prevent BPH in rats by upregulating the PPAR-γ receptor and inhibiting the Wnt pathway.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"225-234"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Canagliflozin: A Comprehensive Review of Advances in Preclinical Research. 卡格列净:临床前研究进展综述。
IF 1.7
Drug Research Pub Date : 2025-07-01 Epub Date: 2025-04-28 DOI: 10.1055/a-2577-1899
Bushra Imran, Farogh Ahsan, Tarique Mahmood, Mohd Masih Uzzaman Khan, Shahzadi Bano, Syed Mehdi Hasan Zaidi, Jamal Akhtar Ansari, Aditya Singh
{"title":"Canagliflozin: A Comprehensive Review of Advances in Preclinical Research.","authors":"Bushra Imran, Farogh Ahsan, Tarique Mahmood, Mohd Masih Uzzaman Khan, Shahzadi Bano, Syed Mehdi Hasan Zaidi, Jamal Akhtar Ansari, Aditya Singh","doi":"10.1055/a-2577-1899","DOIUrl":"10.1055/a-2577-1899","url":null,"abstract":"<p><p>Canagliflozin is a synthetic sodium glucose transporter inhibitor (SGLT2i). It is the latest approved class of medicine used in the treatment of type 2 diabetes mellitus. As diabetes is emerging as the most common metabolic disorder, SGLT2i has lightened up the path of treatment with additional benefits. SGLT2 is located in the proximal convoluted tubules of the nephron and is responsible for glucose reabsorption. Thus, inhibiting the SGLT2 leads to a decline in glucose concentration in the plasma. The secondary effects of canagliflozin, such as cardiac protection, renoprotective, and decreased obesity, have made it more putative in the treatment of diabetes mellitus. There are some side effects of canagliflozin, such as volume depletion, genital and urinary tract infection, and lower limb amputation, which could be a matter of concern for patients. Being an anti-diabetic drug, canagliflozin also possesses anti-inflammatory and anti-cancer properties. Several studies have been conducted to determine the efficacy of canagliflozin as an anti-cancer agent. Its pharmacokinetics indicate rapid absorption, reaching peak plasma concentrations within 1-2 hours. With a half-life of approximately 12 hours, it undergoes minimal hepatic metabolism and is primarily excreted unchanged via urine. Common adverse drug reactions (ADRs) include urinary tract infections and dehydration. Clinical trials on canagliflozin, both alone and in combination with other diabetes complications, have been conducted, with some completed and others in various phases. This review article contains information about the pharmacokinetics, drug safety, and efficacy profile of canagliflozin, along with details regarding toxicological studies of canagliflozin.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"183-201"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Infecting Cancer to Cure It: The Power of Oncolytic Viruses in Gynecologic Oncology - A Narrative Review. 感染癌症以治疗癌症:溶瘤病毒在妇科肿瘤中的作用——综述。
IF 1.7
Drug Research Pub Date : 2025-06-10 DOI: 10.1055/a-2618-6935
Naina Kumar
{"title":"Infecting Cancer to Cure It: The Power of Oncolytic Viruses in Gynecologic Oncology - A Narrative Review.","authors":"Naina Kumar","doi":"10.1055/a-2618-6935","DOIUrl":"https://doi.org/10.1055/a-2618-6935","url":null,"abstract":"<p><p>Gynecological cancers, including ovarian, cervical, and endometrial malignancies, contribute significantly to the global cancer burden. Oncolytic virotherapy (OVT), using both double-stranded DNA viruses (such as adenovirus, vaccinia, and herpesvirus) and single-stranded RNA viruses (including positive-sense viruses like coxsackievirus and poliovirus, and negative-sense viruses like measles and Newcastle disease virus), has emerged as a promising therapeutic approach. This review aims to evaluate the current state and future prospects of OVT in treating gynecological cancers.A literature search was conducted from December 2005 to December 2024 using databases like PubMed, Scopus, and Web of Science with keywords such as \"oncolytic virotherapy,\" \"gynecological cancers,\" and specific virus types. Studies were included after assessing the efficacy, safety, mechanisms of action, and combinatorial use of OVT with other therapies. Exclusions included non-English publications, non-gynecological cancer studies, and those without relevant clinical or experimental data. This review thoroughly explores OVT's potential in gynecological cancer treatment.Oncolytic virotherapy demonstrates transformative potential for managing gynecological cancers. Whether used as monotherapy or in combination with other treatments, OVT shows promise in improving therapeutic outcomes and patient survival. However, further research is necessary to optimize its clinical application.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Curcumin in Type 2 Diabetes Mellitus: A Natural Approach to Modulating Metabolic Dysfunction. 2型糖尿病中的姜黄素:调节代谢功能障碍的自然途径。
IF 1.7
Drug Research Pub Date : 2025-06-02 DOI: 10.1055/a-2604-4115
Rufaida Wasim, Sumaiya Azmi, Mohammad Owais, Aamir Anwar
{"title":"Curcumin in Type 2 Diabetes Mellitus: A Natural Approach to Modulating Metabolic Dysfunction.","authors":"Rufaida Wasim, Sumaiya Azmi, Mohammad Owais, Aamir Anwar","doi":"10.1055/a-2604-4115","DOIUrl":"https://doi.org/10.1055/a-2604-4115","url":null,"abstract":"<p><p>A complex and multifaceted metabolic disease, type 2 diabetes mellitus (T2DM) is becoming a significant public health concern. Due to their many biological characteristics, bioactive compounds from herbal medicine have been shown in multiple studies to have positive benefits on the prevention and control of type 2 diabetes. The scientific community is becoming more interested in curcumin, one of these therapeutic herbs. The plant Curcuma longa, often known as turmeric, has a bioactive compound called curcumin in its rhizome. Antioxidant, cardio-protective, anti-inflammatory, anti-microbial, nephro-protective, anti-neoplastic, hepato-protective, immunomodulatory, hypoglycemic, and anti-rheumatic effects are among the various pharmacological and biological effects of curcumin that have been reported by both in vitro and in vivo studies. Curcumin extract increases -cell functioning, delays the onset of diabetes, inhibits -cell death, and lowers insulin resistance in animal models. Recent preclinical studies and clinical trials have shown strong evidence of curcumin's vital roles in preventing type 2 diabetes via a number of pathways. Thus, the antidiabetic action of curcumin and its many mechanisms are comprehensively summarized in this study. The findings indicated that curcumin's anti-inflammatory, anti-oxidant, antihyperglycemic, antiapoptotic, and antihyperlipidemic properties, among others, account for its success in treating type 2 diabetes. These findings suggest that curcumin could be a potential option for T2DM prevention and management.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of Vitamin B6 on the Expression and Development of Tolerance to Morphine Stimulating Effects on Locomotor Activity in Mice. 维生素B6对吗啡刺激小鼠运动活性耐受表达和发展的影响。
IF 1.7
Drug Research Pub Date : 2025-06-01 Epub Date: 2025-03-05 DOI: 10.1055/a-2535-8528
Amir Abbas Barzegari, Maryam Azaddar, Mohammad-Reza Ghiasi, Hassan Sheikhi
{"title":"Effects of Vitamin B6 on the Expression and Development of Tolerance to Morphine Stimulating Effects on Locomotor Activity in Mice.","authors":"Amir Abbas Barzegari, Maryam Azaddar, Mohammad-Reza Ghiasi, Hassan Sheikhi","doi":"10.1055/a-2535-8528","DOIUrl":"10.1055/a-2535-8528","url":null,"abstract":"<p><p>Chronic use of morphine may induce tolerance to its different pharmacological effects. Vitamin B6 has a central role, as a cofactor, in the biosynthesis of neurotransmitters that are involve in morphine's effects. Moreover, this vitamin affects on morphine's reward and analgesic properties. Therefore, the current research aimed to evaluate the effects of vitamin B6 on the expression and acquisition of tolerance to morphine locomotor-stimulating effects.Twenty groups of mice (n=8) were selected randomly. Acute effects of different doses of morphine (1-30 mg/kg) or vitamin B6 (25-75 mg/kg) on locomotor activity were evaluated using an activity meter. Induction of tolerance was conducted using morphine (30 mg/kg)×2 times a day×3 days plus a single dose of morphine (30 mg/kg) on fourth day. In expression experiment, vitamin B6 (25-75 mg/kg) or saline was injected one hour before the last dose morphine, after tolerance induction. In the acquisition test, one hour before each dose of morphine (in the first three days of tolerance induction) saline or vitamin B6 (25-75 mg/kg) was administered to mice.Although vitamin B6 had no effect on locomotion, administration of morphine had a biphasic effect on mice's locomotor activity; it decreased locomotion at a low dose (5 mg/kg) and increased it at a high dose (30 mg/kg). Furthermore, administration of vitamin B6 before morphine could inhibit the expression and the acquisition of tolerance to morphine-stimulating effects on locomotor activity.Vitamin B6 may be considered as a nutritional supplement in reducing morphine tolerance.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"140-147"},"PeriodicalIF":1.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Possible Drug-Drug Interactions Between Mesalamine and Tricyclic Antidepressants Through CYP2D6 Metabolism - In silico and In vitro Analyses. 美沙拉明和三环抗抑郁药通过CYP2D6代谢可能的药物相互作用-计算机和体外分析。
IF 1.7
Drug Research Pub Date : 2025-06-01 Epub Date: 2025-04-01 DOI: 10.1055/a-2551-2418
Melek B Ozen, Isil Gazioglu, Ozden Ozgun Acar, Huseyin Guner, Gurkan Semiz, Alaattin Sen
{"title":"Possible Drug-Drug Interactions Between Mesalamine and Tricyclic Antidepressants Through CYP2D6 Metabolism - In silico and In vitro Analyses.","authors":"Melek B Ozen, Isil Gazioglu, Ozden Ozgun Acar, Huseyin Guner, Gurkan Semiz, Alaattin Sen","doi":"10.1055/a-2551-2418","DOIUrl":"10.1055/a-2551-2418","url":null,"abstract":"<p><p>Mesalamine (mesalazine, 5-aminosalicylic acid, 5-ASA) is an essential anti-inflammatory agent both used for therapy and as a remission control in patients with inflammatory bowel diseases (IBD) such as ulcerative colitis (UC). Tricyclic antidepressants (TCAs) are used to alleviate remaining symptoms in patients already receiving IBD therapy or with quiescent inflammation. The cytochrome P4502D6 enzyme is involved in the metabolism of TCAs. Hence, it is crucial to investigate the role of CYP2D6 in 5-ASA metabolism. Initially, in silico analysis involving the docking of 5-ASA to CYP2D6 and molecular dynamics simulations was conducted. Next, the rate of O-demethylation of a nonfluorescent probe 3-[2-(N,N-diethyl-N-methylammonium)-ethyl]-7-methoxy-4-methylcoumarin (AMMC) into a fluorescent metabolite AMHC (3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-hydroxy-4-methylcoumarin) was optimized with baculosomes co-expressing human CYP2D6 and human P450 oxidoreductase (hCPR) to monitor CYP2D6 activity in a microtiter plate assay. The apparent Km and Vmax were found to be 1.30 μM and 32.68 pmol/min/mg of protein for the O-demethylation of AMMC to AMHC, and the reaction was linear for 40 min. Then, nonselective inhibition of CYP2D6 activity with various concentrations of 5-ASA was detected. Finally, the conversion of AMMC to metabolites was analyzed by HPLC-ESI-MS/MS spectrometry, and none were identified. Thus, this study suggests that concurrent use of mesalamine with TCA may lead to adverse effects, and CYP2D6 genotyping should be routinely performed on these patients to eliminate possible threats.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"169-178"},"PeriodicalIF":1.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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