Pharmaceuticals最新文献

{"title":"Design, Development and Immunogenicity Study of a Multi-Epitope Vaccine Prototype Against SARS-CoV-2.","authors":"Mariyana Atanasova, Ivan Dimitrov, Nikola Ralchev, Aleksandar Markovski, Iliyan Manoylov, Silviya Bradyanova, Nikolina Mihaylova, Andrey Tchorbanov, Irini Doytchinova","doi":"10.3390/ph17111498","DOIUrl":"https://doi.org/10.3390/ph17111498","url":null,"abstract":"<p><p><b>Objectives:</b> SARS-CoV-2 caused the COVID-19 pandemic, which overwhelmed global healthcare systems. Over 776 million COVID-19 cases and more than 7 million deaths were reported by WHO in September 2024. COVID-19 vaccination is crucial for preventing infection and controlling the pandemic. Here, we describe the design and development of a next-generation multi-epitope vaccine for SARS-CoV-2, consisting of T cell epitopes. <b>Methods:</b> Immunoinformatic methods were used to derive models for the selection of MHC binders specific for the mouse strain used in this study among a set of human SARS-CoV-2 T cell epitopes identified in convalescent patients with COVID-19. The immunogenicity of the vaccine prototype was tested on humanized-ACE2 transgenic B6.Cg-Tg(K18-ACE2)2Prlmn/J mice by in vitro, in vivo, and ex vivo immunoassays. <b>Results:</b> Eleven binders (two from the Envelope (E) protein; two from the Membrane (M) protein; three from the Spike (S) protein; and four from the Nucleocapsid (N) protein) were synthesized and included in a multi-epitope vaccine prototype. The animals were immunized with a mix of predicted MHC-I, MHC-II, or MHC-I/MHC-II peptide epitopes in Complete Freund's Adjuvant, and boosted with peptides in Incomplete Freund's Adjuvant. Immunization with SARS-CoV-2 epitopes remodeled the lymphocyte profile. A weak humoral response and the significant production of IL-4 and IFN-γ from T cells were found after the vaccination of the animals. <b>Conclusions:</b> The multi-epitope vaccine prototype presented in this study demonstrates immunogenicity in mice and shows potential for human vaccine construction.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732067","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}

{"title":"Antibacterial Effects of Essential Oils on <i>P. aeruginosa</i>, Methicillin-Resistant <i>S. aureus</i>, and <i>Staphylococcus</i> spp. Isolated from Dog Wounds.","authors":"Merve Gizem Sezener Kabay, Sinem Inal, Sedat Gökmen, Volkan Enes Ergüden, Arzu Fındık, Tolga Güvenç, Hülya Kayhan, Dilek Güvenç","doi":"10.3390/ph17111494","DOIUrl":"https://doi.org/10.3390/ph17111494","url":null,"abstract":"<p><p><b>Background</b>: Essential oils exhibit several biological activities such as antimicrobial, antioxidant, proliferative, and anti-inflammatory. This study was aimed at investigating the antimicrobial effects and cytotoxic activities of niaouli, palmarosa, and clove essential oils. <b>Methods</b>: Content analyses of these essential oils were carried out by gas chromatography-mass spectrometry. The antibacterial activity was screened against methicillin-resistant <i>S. aureus</i> ATCC 43300, <i>P. aeruginosa</i> ATCC 27853, <i>P. aeruginosa</i> PAO1, <i>S. aureus</i> ATCC 25923, and 44 isolates (22 <i>P. aeruginosa</i> isolates, 4 <i>S. aureus</i> isolates, and 18 <i>Staphylococcus</i> spp. isolates) obtained from dogs with previous wound infections who were included in the current study. The antimicrobial effects of essential oils were investigated using disk diffusion and minimum inhibition/bactericidal concentration methods. Additionally, the antibiofilm, protease, elastase, and gelatinase activities of the essential oils were evaluated. Different concentrations of each essential oil ranging from 10 to 1000 µg/mL were also analyzed in terms of cell viability by WST-8 assay in primary canine fibroblast cells. <b>Results:</b> The fibroblast cell viabilities of palmarosa, niaouli, and clove oils at a 1000 µg/mL concentration were 75.4%, 96.39%, and 75.34%, respectively. All the EOs were found to have bactericidal effects with MBCs/MICs of 0.015 to 0.5 µL/mL against <i>P. aeruginosa</i>, <i>Staphylococcus</i> isolates (<i>p</i> < 0.001). Palmarosa was found to have the largest inhibition zone diameter (20.5 ± 6.6, 16.4 ± 2.3) compared to other essential oils in the disk diffusion test against <i>Staphylococcus</i> spp. and <i>P. aeruginosa</i> (<i>p</i> < 0.001). But none of the EOs reduced protease, elastase, and gelatinase activities, which are some of the virulence properties of the tested bacteria. <b>Conclusions:</b> These results showed that palmarosa, niaouli, and clove essential oils act as potential antibacterial agents for dogs against <i>P. aeruginosa</i>, methicillin-resistant <i>S. aureus</i>, and <i>Staphylococcus</i> spp., without damaging the skin.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731770","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}

{"title":"Adequacy of Anesthesia Guidance for Combined General/Epidural Anesthesia in Patients Undergoing Open Abdominal Infrarenal Aortic Aneurysm Repair; Preliminary Report on Hemodynamic Stability and Pain Perception.","authors":"Michał Jan Stasiowski, Seweryn Król, Paweł Wodecki, Nikola Zmarzły, Beniamin Oskar Grabarek","doi":"10.3390/ph17111497","DOIUrl":"https://doi.org/10.3390/ph17111497","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Hemodynamic instability and inappropriate postoperative pain perception (IPPP) with their consequences constitute an anesthesiological challenge in patients undergoing primary elective open lumbar infrarenal aortic aneurysm repair (OLIAAR) under general anesthesia (GA), as suboptimal administration of intravenous rescue opioid analgesics (IROAs), whose titration is optimized by Adequacy of Anaesthesia (AoA) guidance, constitutes a risk of adverse events. Intravenous or thoracic epidural anesthesia (TEA) techniques of preventive analgesia have been added to GA to minimize these adverse events. <b>Methods</b>: Seventy-five patients undergoing OLIAAR were randomly assigned to receive TEA with 0.2% ropivacaine (RPV) with fentanyl (FNT) 2.5 μg/mL (RPV group) or 0.2% bupivacaine (BPV) with FNT 2.5 μg/mL (BPV group) or intravenous metamizole/tramadol (MT group). IROA using FNT during GA was administered under AoA guidance. Systemic morphine was administered as a rescue agent in all groups postoperatively in the case of IPPP, assessed using the Numeric Pain Rating Score > 3. The maximum score at admission and the minimum at discharge from the postoperative care unit to the Department of Vascular Surgery, perioperative hemodynamic stability, and demand for rescue opioid analgesia were analyzed. <b>Results</b>: Ultimately, 57 patients were analyzed. In 49% of patients undergoing OLIAAR, preventive analgesia did not prevent the incidence of IPPP, which was not statistically significant between groups. No case of acute postoperative pain perception was noted in the RPV group, but at the cost of statistically significant minimum mean arterial pressure values, reflecting hemodynamic instability, with clinical significance < 65mmHg. Demand for postoperative morphine was not statistically significantly different between groups, contrary to significantly lower doses of IROA using FNT in patients receiving TEA. <b>Conclusions</b>: AoA guidance for IROA administration with FNT blunted the preventive analgesia effect of TEA compared with intravenous MT that ensured proper perioperative hemodynamic stability along with adequate postoperative pain control with acceptable demand for postoperative morphine.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731384","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}

{"title":"Therapies for Chronic Spontaneous Urticaria: Present and Future Developments.","authors":"Riccardo Asero, Paolo Calzari, Silvia Vaienti, Massimo Cugno","doi":"10.3390/ph17111499","DOIUrl":"https://doi.org/10.3390/ph17111499","url":null,"abstract":"<p><p>Chronic spontaneous urticaria (CSU) is a complex dermatological condition characterized by recurrent wheals and/or angioedema lasting for more than six weeks, significantly impairing patients' quality of life. According to European guidelines, the first step in treatment involves second-generation H1-antihistamines (sgAHs), which block peripheral H1 receptors to alleviate symptoms. In cases with inadequate responses, the dose of antihistamines can be increased by up to fourfold. If symptoms persist despite this adjustment, the next step involves the use of omalizumab, a monoclonal anti-IgE antibody, which has shown efficacy in the majority of cases. However, a subset of patients remains refractory, necessitating alternative treatments such as immunosuppressive agents like cyclosporine or azathioprine. To address these unmet needs, several new therapeutic targets are being explored. Among them, significant attention is being given to drugs that block Bruton's tyrosine kinase (BTK), such as remibrutinib, which reduces mast cell activation. Therapies like dupilumab, which target the interleukin-4 (IL-4) and IL-13 pathways, are also under investigation. Additionally, molecules targeting the Mas-related G protein-coupled receptor X2 (MRGPRX2), and those inhibiting the tyrosine kinase receptor Kit, such as barzolvolimab, show promise in clinical studies. These emerging treatments offer new options for patients with difficult-to-treat CSU and have the potential to modify the natural course of the disease by targeting key immune pathways, helping to achieve longer-term remission. Further research is essential to better elucidate the pathophysiology of CSU and optimize treatment protocols to achieve long-term benefits in managing this condition. Altogether, the future of CSU treatments that target pathogenetic mechanisms seems promising.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732012","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}

{"title":"From Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1.","authors":"Martin Law, Pei-Chun Wang, Zhong-Yan Zhou, Yu Wang","doi":"10.3390/ph17111495","DOIUrl":"https://doi.org/10.3390/ph17111495","url":null,"abstract":"<p><p>Silent information regulator sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase with potent anti-arterial aging activities. Its protective function in aging-related diseases has been extensively studied. In the microcirculation, SIRT1 plays a crucial role in preventing microcirculatory endothelial senescence by suppressing inflammation and oxidative stress while promoting mitochondrial function and optimizing autophagy. It suppresses hypoxia-inducible factor-1α (HIF-1α)-mediated pathological angiogenesis while promoting healthy, physiological capillarization. As a result, SIRT1 protects against microvascular dysfunction, such as diabetic microangiopathy, while enhancing exercise-induced skeletal muscle capillarization and energy metabolism. In the brain, SIRT1 upregulates tight junction proteins and strengthens their interactions, thus maintaining the integrity of the blood-brain barrier. The present review summarizes recent findings on the regulation of microvascular function by SIRT1, the underlying mechanisms, and various approaches to modulate SIRT1 activity in microcirculation. The importance of SIRT1 as a molecular target in aging-related diseases, such as diabetic retinopathy and stroke, is underscored, along with the need for more clinical evidence to support SIRT1 modulation in the microcirculation.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731890","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}

{"title":"<i>Vernonanthura tweediana</i> (Baker) H. Rob. (Asteraceae), an Ordinary Bush or an Anti-Inflammatory and Immunomodulator Aromatic Species?","authors":"Isabel D Machado, Pâmela P Borges, Larissa J A Giacomozzi, Larissa Benvenutti, José R Santin, Sarah C Dos Santos, Martinho Rau, Iêda M Begnini, Ricardo A Rebelo, Henrique D M Coutinho, Clara M G Lima, Talha B Emran","doi":"10.3390/ph17111492","DOIUrl":"https://doi.org/10.3390/ph17111492","url":null,"abstract":"<p><p><b>Background:</b> Oral traditional knowledge disseminates the use of young leaves of <i>Vernonanthura tweediana</i> (Asteraceae) as poultice in feverish cases among family farmers in Santa Catarina, Brazil, but there is a lack of phytochemistry and pharmacological studies on this species, especially those related to volatile organic compounds. <b>Methods:</b> In the present study, the dry leaves of <i>V. tweediana</i> were subjected to hydrodistillation for the extraction of essential oil. Sample characterization was conducted using GC-FID and GC-MS. To evaluate anti-inflammatory and immunomodulatory activities, the air pouch method was used, and with the exudate obtained, total and differential leukocyte counts were performed, as well as the quantification of total proteins, interleukin (IL) 1β, IL-6, and tumor necrosis factor (TNF). <b>Results:</b> The essential oil yield extraction was 0.13%, and sesquiterpenes were the main constituents: α-copaene (5.1%), β-caryophyllene (27.77%), α-caryophyllene (15.1%), germacrene D (14.0%), and bicyclogermacrene (13.3%). A sample was subjected to biological tests, with a reduction in leukocyte migration to the inflammatory focus. The immunomodulatory activity was also pronounced, as the oil modulated all cytokine secretions measured when compared to the control. The high concentration of caryophyllenes might explain these findings. <b>Conclusions:</b> Future studies will consider the fractionation of the essential oil to establish the degree of synergism between the constituents.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731971","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}

{"title":"Advances in Loading Techniques and Quality by Design for Fused Deposition Modeling in Pharmaceutical Production: A Systematic Review.","authors":"Yusra Ahmed, Azza A K Mahmoud, Krisztina Ludasi, Tamás Sovány","doi":"10.3390/ph17111496","DOIUrl":"https://doi.org/10.3390/ph17111496","url":null,"abstract":"<p><strong>Background/objectives: </strong>Three-dimensional printing technology has emerging interest in pharmaceutical manufacturing, offering new opportunities for personalized medicine and customized drug delivery systems. Fused deposition modeling (FDM) is highly regarded in the pharmaceutical industry because of its cost effectiveness, easy operation, and versatility in creating pharmaceutical dosage forms. This review investigates different methods of incorporating active pharmaceutical ingredients (APIs) into filament matrices for use in fused deposition modeling (FDM) 3D printing.</p><p><strong>Methods: </strong>Two electronic databases, the Web of Science and PubMed, were utilized to survey the literature. The selected keywords for this review were as follows: fused filament fabrication OR fused deposition modeling OR FDM OR FFF AND 3D printing AND loading techniques OR impregnation techniques AND solid dosage form.</p><p><strong>Results: </strong>This paper evaluates various loading techniques such as soaking, supercritical impregnation, microwave impregnation, and hot-melt extrusion, focusing on their effectiveness and capacity for drug incorporation. Additionally, this review includes a thorough risk assessment of the extrusion process using Ishikawa and SWOT analyses.</p><p><strong>Conclusions: </strong>Overall, this review provides comprehensive insights into the latest advancements in 3D printing for pharmaceutical applications and identifies key areas for future research and development.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731616","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}

{"title":"Neuroprotective Potential of Glycyrrhizic Acid in Ischemic Stroke: Mechanisms and Therapeutic Prospects.","authors":"Yanwen Li, Juan Wu, Fang Du, Tao Tang, Jonathan Chee Woei Lim, Thilakavathy Karuppiah, Jiaxin Liu, Zhong Sun","doi":"10.3390/ph17111493","DOIUrl":"https://doi.org/10.3390/ph17111493","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Ischemic stroke is a leading cause of disability and mortality worldwide, with current therapies limited in addressing its complex pathophysiological mechanisms, such as inflammation, oxidative stress, apoptosis, and impaired autophagy. Glycyrrhizic acid (GA), a bioactive compound from licorice (<i>Glycyrrhiza glabra</i> L.), has demonstrated neuroprotective properties in preclinical studies. This review consolidates current evidence on GA's pharmacological mechanisms and assesses its potential as a therapeutic agent for ischemic stroke. <b>Methods</b>: This review examines findings from recent preclinical studies and reviews on GA's neuroprotective effects, focusing on its modulation of inflammation, oxidative stress, apoptosis, and autophagy. Studies were identified from major scientific databases, including PubMed, Web of Science, and Embase, covering research from January 2000 to August 2024. <b>Results</b>: GA has demonstrated significant neuroprotective effects through the modulation of key pathways, including HMGB1/TLR4/NF-κB and Keap1/Nrf2, thereby reducing neuroinflammation, oxidative stress, and apoptosis. Additionally, GA promotes autophagy and modulates immune responses, suggesting it could serve as an adjunct therapy to enhance the efficacy and safety of existing treatments, such as thrombolysis. <b>Conclusions</b>: Current findings underscore GA's potential as a multi-targeted neuroprotective agent in ischemic stroke, highlighting its anti-inflammatory, antioxidant, and anti-apoptotic properties. However, while preclinical data are promising, further clinical trials are necessary to validate GA's therapeutic potential in humans. This review provides a comprehensive overview of GA's mechanisms of action, proposing directions for future research to explore its role in ischemic stroke management.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731853","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}

{"title":"Analysis of Adverse Reactions Associated with the Use of <i>Crataegus</i>-Containing Herbal Products.","authors":"Herman J Woerdenbag, Melissa Ursidae, Corine Ekhart, Martina Schmidt, Annabella Vitalone, Florence P A M van Hunsel","doi":"10.3390/ph17111490","DOIUrl":"https://doi.org/10.3390/ph17111490","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Products from various parts of <i>Crataegus</i> species are traditionally applied as a cardiotonic. In Europe and the USA, mainly <i>Crataegus monogyna</i> Jacq. (Lindm.) and <i>Crataegus laevigata</i> (Poir.) DC (synonym <i>Crataegus oxyacantha</i> L.) are used, but worldwide, other <i>Crataegus</i> species are also used. Phytotherapeutic preparations with a standardised content of flavonoids and/or oligomeric procyanidins are commercially available. The products are generally considered as safe and are at most associated with minor and atypical adverse reactions. The aim of this study was to critically assess the information about the safety of <i>Crataegus</i>-containing products in humans. <b>Methods:</b> A scoping review of the literature about adverse reactions associated with <i>Crataegus</i>-containing products was performed. Next, individual case safety reports (ICSRs) were assessed, which were included in VigiBase (the World Health Organisation's global database of adverse event reports for medicines and vaccines) and in the database of the Netherlands Pharmacovigilance Centre Lareb. The findings are discussed in relation to the literature. <b>Results:</b> The scoping review yielded 23 clinical studies with single-herb and 14 with multi-herb preparations, from which only a few minor gastrointestinal and cardiac events had been reported. A total of 1527 reports from VigiBase, from 1970 to 2023, were analysed, as well as 13 reports from Lareb. The most frequently reported adverse reactions belonged to the system organ classes 'gastrointestinal disorders', 'skin and subcutaneous tissue disorders', 'general disorders and administration site conditions', 'cardiac disorders' or 'nervous system disorders'. In 277 reports of VigiBase, a single-herb product was the only suspect for causing the adverse reaction(s). Of these, 12.6% were graded as serious. <b>Conclusions:</b> The results of our study provide deeper insight in the adverse reaction profile of <i>Crataegus</i>-containing products and should contribute to their safe application in the treatment of less severe forms of cardiac failure.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731848","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}

{"title":"In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine/Sulfonamide Hybrids Targeting Topoisomerases I and II.","authors":"Mohamed Badr, Elshaymaa I Elmongy, Doaa Elkhateeb, Yasmine S Moemen, Ashraf Khalil, Hadeer Ali, Reem Binsuwaidan, Feby Awadallah, Ibrahim El Tantawy El Sayed","doi":"10.3390/ph17111487","DOIUrl":"https://doi.org/10.3390/ph17111487","url":null,"abstract":"<p><strong>Background: </strong>Sulfonamide acridine derivatives have garnered significant attention from medicinal chemists due to their diverse range of biological activities.</p><p><strong>Methods: </strong>In this study, eleven compounds were synthesized according to the literature, and their impact on cell growth inhibition, induction of apoptosis, and cell cycle distribution were assessed in three different cell lines. Their inhibitory effects on the topoisomerase (Topo) I and II were investigated in vitro. Molecular docking studies were conducted to predict the binding affinities of these compounds for crystallized downloaded topoisomerases.</p><p><strong>Results: </strong>The compounds were examined in vitro for their anticancer activity against human hepatic (HepG2) colon (HCT-8) and breast (MCF-7) carcinoma cell lines. Compound <b>8b</b> was the most active against HepG2, HCT-116, and MCF-7 with IC₅₀ 14.51, 9.39, and 8.83 µM, respectively, compared to Doxorubicin as reference. In addition, it demonstrated the highest potency among the tested compounds against Topo-I, with an IC₅₀ value of 3.41 µg/mL compared to the control camptothecin (IC₅₀ of 1.46 μM). Compound <b>7c</b> displayed a significant inhibitory effect on Topo-II, with an IC₅₀ of 7.33 μM, compared to an IC₅₀ value of 6.49 μM via Doxorubicin, the control. Compounds <b>7c</b> and <b>8b</b> were assessed against topoisomerases showing induction of apoptosis and a reduction in the S phase of the cell cycle. Molecular docking demonstrated interaction with the active site as with those exhibited by the co-crystallized ligands of the crystallized proteins in both topoisomerases.</p><p><strong>Conclusion: </strong>Compounds <b>7c</b> and <b>8b</b> hold promise as potential anticancer drugs due to their anti-proliferative and proapoptotic effects, which are mediated by their action on the topoisomerase enzyme, particularly Topo II.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731887","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}