J. T. De Pourcq, Adria Riera, Laura Gras, N. Garin, M. Antònia Busquets, J. Cardenete, Daniel Cardona, P. Riera
Ceftolozane-tazobactam (CT) is used for the treatment of complicated infections and for multidrug-resistant strains of Pseudomonas aeruginosa and extended-spectrum beta-lactamase-producing enterobacteria. In certain cases, simultaneous administration of CT and parenteral nutrition (PN) may be required, but compatibility of Y-site co-administration is unknown. The aim of this study was to analyse the physicochemical compatibility of CT Y-site administered with PN. We evaluated a protocolized PN approach for critical patients in our center. We studied both bolus infusion (2 g ceftolozane/1 g tazobactam in 1 h) and continuous infusion (CI) (6 g ceftolozane/3 g tazobactam) strategies. Samples were visually observed against light, microscopically inspected, and pH was analysed using a pH meter. The mean lipid droplet diameter (MDD) was determined via dynamic light scattering. CT concentration was quantified using HPLC–HRMS. No alterations were observed through visual or microscopic inspection. Changes in pH were ≤0.2, and changes in osmolarity were less than 5%. MDD remained below 500 nm (284.5 ± 2.1 for bolus CT and 286.8 ± 7.5 for CI CT). CT concentrations at t = 0 h and t = 24 h remained within prespecified parameters in both infusion strategies. CT is physiochemically compatible with PN during simulated Y-site administration at the tested concentration and infusion rates.
{"title":"Physicochemical Compatibility of Ceftolozane-Tazobactam with Parenteral Nutrition","authors":"J. T. De Pourcq, Adria Riera, Laura Gras, N. Garin, M. Antònia Busquets, J. Cardenete, Daniel Cardona, P. Riera","doi":"10.3390/ph17070896","DOIUrl":"https://doi.org/10.3390/ph17070896","url":null,"abstract":"Ceftolozane-tazobactam (CT) is used for the treatment of complicated infections and for multidrug-resistant strains of Pseudomonas aeruginosa and extended-spectrum beta-lactamase-producing enterobacteria. In certain cases, simultaneous administration of CT and parenteral nutrition (PN) may be required, but compatibility of Y-site co-administration is unknown. The aim of this study was to analyse the physicochemical compatibility of CT Y-site administered with PN. We evaluated a protocolized PN approach for critical patients in our center. We studied both bolus infusion (2 g ceftolozane/1 g tazobactam in 1 h) and continuous infusion (CI) (6 g ceftolozane/3 g tazobactam) strategies. Samples were visually observed against light, microscopically inspected, and pH was analysed using a pH meter. The mean lipid droplet diameter (MDD) was determined via dynamic light scattering. CT concentration was quantified using HPLC–HRMS. No alterations were observed through visual or microscopic inspection. Changes in pH were ≤0.2, and changes in osmolarity were less than 5%. MDD remained below 500 nm (284.5 ± 2.1 for bolus CT and 286.8 ± 7.5 for CI CT). CT concentrations at t = 0 h and t = 24 h remained within prespecified parameters in both infusion strategies. CT is physiochemically compatible with PN during simulated Y-site administration at the tested concentration and infusion rates.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":" 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141675958","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}
M. Spampinato, T. Zuppelli, I. Dulcamare, L. Longhitano, Domenico Sambataro, Annalisa Santisi, A. M. Alanazi, I. Barbagallo, N. Vicario, R. Parenti, A. Romano, G. Musumeci, Giovanni Li Volti, G. A. Palumbo, F. Di Raimondo, Anna Nicolosi, S. Giallongo, V. Del Fabro
Background: Chronic myeloid leukemia is a hematological malignancy characterized by the abnormal proliferation of leukemic cells. Despite significant progress with tyrosine kinase inhibitors, such as Dasatinib, resistance remains a challenge. The aim of the present study was to investigate the potential of Selinexor, an Exportin-1 inhibitor, to improve TKI effectiveness on CML. Methods: Human CML cell lines (LAMA84 and K562) were treated with Selinexor, Dasatinib, or their combination. Apoptosis, mitochondrial membrane potential, and mitochondrial mass were assessed using flow cytometry. Real-time RT-PCR was used to evaluate the expression of genes related to mitochondrial function. Western blot and confocal microscopy examined PINK and heme oxygenase-1 (HO-1) protein levels. Results: Selinexor induced apoptosis and mitochondrial depolarization in CML cell lines, reducing cell viability. The Dasatinib/Selinexor combination further enhanced cytotoxicity, modified mitochondrial fitness, and downregulated HO-1 nuclear translocation, which has been associated with drug resistance in different models. Conclusions: In conclusion, this study suggests that Dasatinib/Selinexor could be a promising therapeutic strategy for CML, providing new insights for new targeted therapies.
{"title":"Enhanced Antitumor Activity by the Combination of Dasatinib and Selinexor in Chronic Myeloid Leukemia","authors":"M. Spampinato, T. Zuppelli, I. Dulcamare, L. Longhitano, Domenico Sambataro, Annalisa Santisi, A. M. Alanazi, I. Barbagallo, N. Vicario, R. Parenti, A. Romano, G. Musumeci, Giovanni Li Volti, G. A. Palumbo, F. Di Raimondo, Anna Nicolosi, S. Giallongo, V. Del Fabro","doi":"10.3390/ph17070894","DOIUrl":"https://doi.org/10.3390/ph17070894","url":null,"abstract":"Background: Chronic myeloid leukemia is a hematological malignancy characterized by the abnormal proliferation of leukemic cells. Despite significant progress with tyrosine kinase inhibitors, such as Dasatinib, resistance remains a challenge. The aim of the present study was to investigate the potential of Selinexor, an Exportin-1 inhibitor, to improve TKI effectiveness on CML. Methods: Human CML cell lines (LAMA84 and K562) were treated with Selinexor, Dasatinib, or their combination. Apoptosis, mitochondrial membrane potential, and mitochondrial mass were assessed using flow cytometry. Real-time RT-PCR was used to evaluate the expression of genes related to mitochondrial function. Western blot and confocal microscopy examined PINK and heme oxygenase-1 (HO-1) protein levels. Results: Selinexor induced apoptosis and mitochondrial depolarization in CML cell lines, reducing cell viability. The Dasatinib/Selinexor combination further enhanced cytotoxicity, modified mitochondrial fitness, and downregulated HO-1 nuclear translocation, which has been associated with drug resistance in different models. Conclusions: In conclusion, this study suggests that Dasatinib/Selinexor could be a promising therapeutic strategy for CML, providing new insights for new targeted therapies.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":" 45","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141673612","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}
Bruna R. Kouba, Glorister A. Altê, A. L. S. Rodrigues
Depression and anxiety disorders, prevalent neuropsychiatric conditions that frequently coexist, limit psychosocial functioning and, consequently, the individual’s quality of life. Since the pharmacological treatment of these disorders has several limitations, the search for effective and secure antidepressant and anxiolytic compounds is welcome. Vitamin D has been shown to exhibit neuroprotective, antidepressant, and anxiolytic properties. Therefore, this study aimed to explore new molecular targets of calcitriol, the active form of vitamin D, through integrated bioinformatic analysis. Calcitriol targets were predicted in SwissTargetPrediction server (2019 version). The disease targets were collected by the GeneCards database searching the keywords “depression” and “anxiety”. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the intersections of targets. Network analyses were carried out using GeneMania server (2023 version) and Cytoscape (V. 3.9.1.) software. Molecular docking predicted the main targets of the network and Ligplot predicted the main intermolecular interactions. Our study showed that calcitriol may interact with multiple targets. The main targets found are the vitamin D receptor (VDR), histamine H3 receptor (H3R), endocannabinoid receptors 1 and 2 (CB1 and CB2), nuclear receptor NR1H3, patched-1 (PTCH1) protein, opioid receptor NOP, and phosphodiesterase enzymes PDE3A and PDE5A. Considering the role of these targets in the pathophysiology of depression and anxiety, our findings suggest novel putative mechanisms of action of vitamin D as well as new promising molecular targets whose role in these disorders deserves further investigation.
抑郁症和焦虑症是经常并存的神经精神疾病，它们限制了患者的社会心理功能，从而影响了患者的生活质量。由于这些疾病的药物治疗存在一些局限性，因此，寻找有效、安全的抗抑郁和抗焦虑化合物的工作备受欢迎。维生素 D 已被证明具有神经保护、抗抑郁和抗焦虑的特性。因此，本研究旨在通过综合生物信息学分析，探索降钙三醇（维生素 D 的活性形式）的新分子靶点。降钙三醇靶点是在SwissTargetPrediction服务器（2019年版）上预测的。疾病靶点由基因卡片数据库收集，搜索关键词为 "抑郁 "和 "焦虑"。基因本体（GO）和京都基因和基因组百科全书（KEGG）用于分析靶点的交叉。使用 GeneMania 服务器（2023 版）和 Cytoscape（V. 3.9.1.）软件进行网络分析。分子对接预测了网络中的主要靶标，Ligplot 预测了主要的分子间相互作用。我们的研究表明，降钙三醇可能与多个靶点相互作用。发现的主要靶点包括维生素D受体（VDR）、组胺H3受体（H3R）、内源性大麻素受体1和2（CB1和CB2）、核受体NR1H3、patched-1（PTCH1）蛋白、阿片受体NOP以及磷酸二酯酶PDE3A和PDE5A。考虑到这些靶点在抑郁症和焦虑症的病理生理学中的作用，我们的研究结果提出了维生素 D 的新的假定作用机制以及新的有希望的分子靶点，这些靶点在这些疾病中的作用值得进一步研究。
{"title":"Putative Pharmacological Depression and Anxiety-Related Targets of Calcitriol Explored by Network Pharmacology and Molecular Docking","authors":"Bruna R. Kouba, Glorister A. Altê, A. L. S. Rodrigues","doi":"10.3390/ph17070893","DOIUrl":"https://doi.org/10.3390/ph17070893","url":null,"abstract":"Depression and anxiety disorders, prevalent neuropsychiatric conditions that frequently coexist, limit psychosocial functioning and, consequently, the individual’s quality of life. Since the pharmacological treatment of these disorders has several limitations, the search for effective and secure antidepressant and anxiolytic compounds is welcome. Vitamin D has been shown to exhibit neuroprotective, antidepressant, and anxiolytic properties. Therefore, this study aimed to explore new molecular targets of calcitriol, the active form of vitamin D, through integrated bioinformatic analysis. Calcitriol targets were predicted in SwissTargetPrediction server (2019 version). The disease targets were collected by the GeneCards database searching the keywords “depression” and “anxiety”. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the intersections of targets. Network analyses were carried out using GeneMania server (2023 version) and Cytoscape (V. 3.9.1.) software. Molecular docking predicted the main targets of the network and Ligplot predicted the main intermolecular interactions. Our study showed that calcitriol may interact with multiple targets. The main targets found are the vitamin D receptor (VDR), histamine H3 receptor (H3R), endocannabinoid receptors 1 and 2 (CB1 and CB2), nuclear receptor NR1H3, patched-1 (PTCH1) protein, opioid receptor NOP, and phosphodiesterase enzymes PDE3A and PDE5A. Considering the role of these targets in the pathophysiology of depression and anxiety, our findings suggest novel putative mechanisms of action of vitamin D as well as new promising molecular targets whose role in these disorders deserves further investigation.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":" 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141674268","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}
Bruna Michele A. de B. Buriti, P. L. Figueiredo, M. F. Passos, J. D. da Silva
Wound healing can result in complex problems, and discovering an effective method to improve the healing process is essential. Polymeric biomaterials have structures similar to those identified in the extracellular matrix of the tissue to be regenerated and also avoid chronic inflammation, and immunological reactions. To obtain smart and effective dressings, bioactive agents, such as essential oils, are also used to promote a wide range of biological properties, which can accelerate the healing process. Therefore, we intend to explore advances in the potential for applying hybrid materials in wound healing. For this, fifty scientific articles dated from 2010 to 2023 were investigated using the Web of Science, Scopus, Science Direct, and PubMed databases. The principles of the healing process, use of polymers, type and properties of essential oils and processing techniques, and characteristics of dressings were identified. Thus, the plants Syzygium romanticum or Eugenia caryophyllata, Origanum vulgare, and Cinnamomum zeylanicum present prospects for application in clinical trials due to their proven effects on wound healing and reducing the incidence of inflammatory cells in the site of injury. The antimicrobial effect of essential oils is mainly due to polyphenols and terpenes such as eugenol, cinnamaldehyde, carvacrol, and thymol.
伤口愈合可能导致复杂的问题，因此必须找到一种有效的方法来改善愈合过程。高分子生物材料具有与待再生组织细胞外基质相似的结构，还能避免慢性炎症和免疫反应。为了获得智能、有效的敷料，我们还使用了生物活性剂（如精油）来促进各种生物特性，从而加快愈合过程。因此，我们打算探索在伤口愈合中应用混合材料的潜力。为此，我们使用 Web of Science、Scopus、Science Direct 和 PubMed 数据库调查了 2010 年至 2023 年的 50 篇科学文章。确定了愈合过程的原理、聚合物的使用、精油的类型和特性、加工技术以及敷料的特点。因此，浪漫草（Syzygium romanticum）或欧栀子（Eugenia caryophyllata）、牛至（Origanum vulgare）和肉桂（Cinnamomum zeylanicum）等植物被证明对伤口愈合和减少受伤部位炎症细胞的发生率有显著效果，有望应用于临床试验。精油的抗菌作用主要来自多酚和萜烯，如丁香酚、肉桂醛、香芹酚和百里酚。
{"title":"Polymer-Based Wound Dressings Loaded with Essential Oil for the Treatment of Wounds: A Review","authors":"Bruna Michele A. de B. Buriti, P. L. Figueiredo, M. F. Passos, J. D. da Silva","doi":"10.3390/ph17070897","DOIUrl":"https://doi.org/10.3390/ph17070897","url":null,"abstract":"Wound healing can result in complex problems, and discovering an effective method to improve the healing process is essential. Polymeric biomaterials have structures similar to those identified in the extracellular matrix of the tissue to be regenerated and also avoid chronic inflammation, and immunological reactions. To obtain smart and effective dressings, bioactive agents, such as essential oils, are also used to promote a wide range of biological properties, which can accelerate the healing process. Therefore, we intend to explore advances in the potential for applying hybrid materials in wound healing. For this, fifty scientific articles dated from 2010 to 2023 were investigated using the Web of Science, Scopus, Science Direct, and PubMed databases. The principles of the healing process, use of polymers, type and properties of essential oils and processing techniques, and characteristics of dressings were identified. Thus, the plants Syzygium romanticum or Eugenia caryophyllata, Origanum vulgare, and Cinnamomum zeylanicum present prospects for application in clinical trials due to their proven effects on wound healing and reducing the incidence of inflammatory cells in the site of injury. The antimicrobial effect of essential oils is mainly due to polyphenols and terpenes such as eugenol, cinnamaldehyde, carvacrol, and thymol.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":" 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141674765","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}
The efforts to discover HIV therapeutics have continued since the first human immunodeficiency virus (HIV) infected patient was confirmed in the 1980s. Ten years later, the first HIV drug, zidovudine (AZT), targeting HIV reverse transcriptase, was developed. Meanwhile, scientists were enlightened to discover new drugs that target different HIV genes, like integrase, protease, and host receptors. Combination antiretroviral therapy (cART) is the most feasible medical intervention to suppress the virus in people with HIV (PWH) and control the epidemic. ART treatment has made HIV a chronic infection rather than a fatal disease, but ART does not eliminate latent reservoirs of HIV-1 from the host cells; strict and life-long adherence to ART is required for the therapy to be effective in patients. In this review, we first discussed the scientific history of conventional HIV drug discovery since scientists need to develop more and more drugs to solve drug-resistant issues and release the side effects. Then, we summarized the novel research technologies, like gene editing, applied to HIV treatment and their contributions to eliminating HIV as a complementary therapy.
自 20 世纪 80 年代确诊第一例人类免疫缺陷病毒（HIV）感染者以来，人们一直在努力探索 HIV 治疗方法。十年后，第一种针对艾滋病病毒逆转录酶的药物齐多夫定（AZT）问世。与此同时，科学家们发现了针对不同艾滋病毒基因（如整合酶、蛋白酶和宿主受体）的新药。联合抗逆转录病毒疗法（cART）是抑制艾滋病病毒感染者（PWH）体内病毒并控制疫情的最可行的医疗干预措施。抗逆转录病毒疗法使艾滋病成为一种慢性感染而非致命疾病，但抗逆转录病毒疗法并不能消除宿主细胞中潜伏的HIV-1病毒库；患者必须严格并终身坚持抗逆转录病毒疗法才能使治疗有效。在这篇综述中，我们首先讨论了传统 HIV 药物发现的科学史，因为科学家们需要开发越来越多的药物来解决耐药性问题并释放副作用。然后，我们总结了应用于艾滋病治疗的基因编辑等新型研究技术，以及它们作为一种辅助疗法对消除艾滋病病毒所做的贡献。
{"title":"Development of Anti-HIV Therapeutics: From Conventional Drug Discovery to Cutting-Edge Technology","authors":"Yaping Sun, Lingyun Wang","doi":"10.3390/ph17070887","DOIUrl":"https://doi.org/10.3390/ph17070887","url":null,"abstract":"The efforts to discover HIV therapeutics have continued since the first human immunodeficiency virus (HIV) infected patient was confirmed in the 1980s. Ten years later, the first HIV drug, zidovudine (AZT), targeting HIV reverse transcriptase, was developed. Meanwhile, scientists were enlightened to discover new drugs that target different HIV genes, like integrase, protease, and host receptors. Combination antiretroviral therapy (cART) is the most feasible medical intervention to suppress the virus in people with HIV (PWH) and control the epidemic. ART treatment has made HIV a chronic infection rather than a fatal disease, but ART does not eliminate latent reservoirs of HIV-1 from the host cells; strict and life-long adherence to ART is required for the therapy to be effective in patients. In this review, we first discussed the scientific history of conventional HIV drug discovery since scientists need to develop more and more drugs to solve drug-resistant issues and release the side effects. Then, we summarized the novel research technologies, like gene editing, applied to HIV treatment and their contributions to eliminating HIV as a complementary therapy.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":" 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141678142","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}
Marcos Lorca, Gisela C. Muscia, S. Pérez-Benavente, José M. Bautista, Alison Acosta, Cesar González, Gianfranco Sabadini, J. Mella, S. Asís, Marco Mellado
Malaria is an infectious disease caused by Plasmodium spp. parasites, with widespread drug resistance to most antimalarial drugs. We report the development of two 3D-QSAR models based on comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and a 2D-QSAR model, using a database of 349 compounds with activity against the P. falciparum 3D7 strain. The models were validated internally and externally, complying with all metrics (q2 > 0.5, r2test > 0.6, r2m > 0.5, etc.). The final models have shown the following statistical values: r2test CoMFA = 0.878, r2test CoMSIA = 0.876, and r2test 2D-QSAR = 0.845. The models were experimentally tested through the synthesis and biological evaluation of ten quinoline derivatives against P. falciparum 3D7. The CoMSIA and 2D-QSAR models outperformed CoMFA in terms of better predictive capacity (MAE = 0.7006, 0.4849, and 1.2803, respectively). The physicochemical and pharmacokinetic properties of three selected quinoline derivatives were similar to chloroquine. Finally, the compounds showed low cytotoxicity (IC50 > 100 µM) on human HepG2 cells. These results suggest that the QSAR models accurately predict the toxicological profile, correlating well with experimental in vivo data.
{"title":"2D/3D-QSAR Model Development Based on a Quinoline Pharmacophoric Core for the Inhibition of Plasmodium falciparum: An In Silico Approach with Experimental Validation","authors":"Marcos Lorca, Gisela C. Muscia, S. Pérez-Benavente, José M. Bautista, Alison Acosta, Cesar González, Gianfranco Sabadini, J. Mella, S. Asís, Marco Mellado","doi":"10.3390/ph17070889","DOIUrl":"https://doi.org/10.3390/ph17070889","url":null,"abstract":"Malaria is an infectious disease caused by Plasmodium spp. parasites, with widespread drug resistance to most antimalarial drugs. We report the development of two 3D-QSAR models based on comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and a 2D-QSAR model, using a database of 349 compounds with activity against the P. falciparum 3D7 strain. The models were validated internally and externally, complying with all metrics (q2 > 0.5, r2test > 0.6, r2m > 0.5, etc.). The final models have shown the following statistical values: r2test CoMFA = 0.878, r2test CoMSIA = 0.876, and r2test 2D-QSAR = 0.845. The models were experimentally tested through the synthesis and biological evaluation of ten quinoline derivatives against P. falciparum 3D7. The CoMSIA and 2D-QSAR models outperformed CoMFA in terms of better predictive capacity (MAE = 0.7006, 0.4849, and 1.2803, respectively). The physicochemical and pharmacokinetic properties of three selected quinoline derivatives were similar to chloroquine. Finally, the compounds showed low cytotoxicity (IC50 > 100 µM) on human HepG2 cells. These results suggest that the QSAR models accurately predict the toxicological profile, correlating well with experimental in vivo data.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":" 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141678525","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}
Lilia Chérigo, Javier Liao-Luo, Juan Fernández, Sergio Martínez-Luis
Panama boasts an expansive mangrove area and stands as one of the most biodiverse countries in America. While mangrove plants have long been utilized in traditional medicine, there are still unstudied species whose potential medicinal applications remain unknown. This study aimed to extract bioactive compounds from Mora oleifera (Triana ex Hemsl.) Ducke, an understudied mangrove species. Through bioassay-guided fractionation of the crude extract, we isolated seven active compounds identified as lupenone (1), lupeol (2), α-amyrin (3), β-amyrin (4), palmitic acid (5), sitosterol (6), and stigmasterol (7). Compound structures were determined using spectroscopic analyses, including APCI-HR-MS and NMR. Compounds 1–7 displayed concentration-dependent inhibition of the alpha-glucosidase enzyme, with IC50 values of 0.72, 1.05, 2.13, 1.22, 240.20, 18.70, and 163.10 µM, respectively. Their inhibitory activity surpassed acarbose, the positive control (IC50 241.6 µM). Kinetic analysis revealed that all compounds acted as competitive inhibitors. Docking analysis predicted that all triterpenes bonded to the same site as acarbose in human intestinal alpha-glucosidase (PDB: 3TOP). A complementary metabolomic analysis of M. oleifera active fractions revealed the presence of 64 compounds, shedding new light on the plant’s chemical composition. These findings suggest that M. oleifera holds promise as a valuable botanical source for developing compounds for managing blood sugar levels in individuals with diabetes.
{"title":"Isolation of Alpha-Glucosidase Inhibitors from the Panamanian Mangrove Plant Mora oleifera (Triana ex Hemsl.) Ducke","authors":"Lilia Chérigo, Javier Liao-Luo, Juan Fernández, Sergio Martínez-Luis","doi":"10.3390/ph17070890","DOIUrl":"https://doi.org/10.3390/ph17070890","url":null,"abstract":"Panama boasts an expansive mangrove area and stands as one of the most biodiverse countries in America. While mangrove plants have long been utilized in traditional medicine, there are still unstudied species whose potential medicinal applications remain unknown. This study aimed to extract bioactive compounds from Mora oleifera (Triana ex Hemsl.) Ducke, an understudied mangrove species. Through bioassay-guided fractionation of the crude extract, we isolated seven active compounds identified as lupenone (1), lupeol (2), α-amyrin (3), β-amyrin (4), palmitic acid (5), sitosterol (6), and stigmasterol (7). Compound structures were determined using spectroscopic analyses, including APCI-HR-MS and NMR. Compounds 1–7 displayed concentration-dependent inhibition of the alpha-glucosidase enzyme, with IC50 values of 0.72, 1.05, 2.13, 1.22, 240.20, 18.70, and 163.10 µM, respectively. Their inhibitory activity surpassed acarbose, the positive control (IC50 241.6 µM). Kinetic analysis revealed that all compounds acted as competitive inhibitors. Docking analysis predicted that all triterpenes bonded to the same site as acarbose in human intestinal alpha-glucosidase (PDB: 3TOP). A complementary metabolomic analysis of M. oleifera active fractions revealed the presence of 64 compounds, shedding new light on the plant’s chemical composition. These findings suggest that M. oleifera holds promise as a valuable botanical source for developing compounds for managing blood sugar levels in individuals with diabetes.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":" 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141678168","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}
I. Yamari, Oussama Abchir, H. Nour, Meriem Khedraoui, Bouchra Rossafi, A. Errougui, M. Talbi, Abdelouahid Samadi, M. E. Kouali, S. Chtita
Candida albicans and Aspergillus fumigatus are recognized as significant fungal pathogens, responsible for various human infections. The rapid emergence of drug-resistant strains among these fungi requires the identification and development of innovative antifungal therapies. We undertook a comprehensive screening of 297 naturally occurring compounds to address this challenge. Using computational docking techniques, we systematically analyzed the binding affinity of each compound to key proteins from Candida albicans (PDB ID: 1EAG) and Aspergillus fumigatus (PDB ID: 3DJE). This rigorous in silico examination aimed to unveil compounds that could potentially inhibit the activity of these fungal infections. This was followed by an ADMET analysis of the top-ranked compound, providing valuable insights into the pharmacokinetic properties and potential toxicological profiles. To further validate our findings, the molecular reactivity and stability were computed using the DFT calculation and molecular dynamics simulation, providing a deeper understanding of the stability and behavior of the top-ranking compounds in a biological environment. The outcomes of our study identified a subset of natural compounds that, based on our analysis, demonstrate notable potential as antifungal candidates. With further experimental validation, these compounds could pave the way for new therapeutic strategies against drug-resistant fungal pathogens.
{"title":"Unveiling Moroccan Nature’s Arsenal: A Computational Molecular Docking, Density Functional Theory, and Molecular Dynamics Study of Natural Compounds against Drug-Resistant Fungal Infections","authors":"I. Yamari, Oussama Abchir, H. Nour, Meriem Khedraoui, Bouchra Rossafi, A. Errougui, M. Talbi, Abdelouahid Samadi, M. E. Kouali, S. Chtita","doi":"10.3390/ph17070886","DOIUrl":"https://doi.org/10.3390/ph17070886","url":null,"abstract":"Candida albicans and Aspergillus fumigatus are recognized as significant fungal pathogens, responsible for various human infections. The rapid emergence of drug-resistant strains among these fungi requires the identification and development of innovative antifungal therapies. We undertook a comprehensive screening of 297 naturally occurring compounds to address this challenge. Using computational docking techniques, we systematically analyzed the binding affinity of each compound to key proteins from Candida albicans (PDB ID: 1EAG) and Aspergillus fumigatus (PDB ID: 3DJE). This rigorous in silico examination aimed to unveil compounds that could potentially inhibit the activity of these fungal infections. This was followed by an ADMET analysis of the top-ranked compound, providing valuable insights into the pharmacokinetic properties and potential toxicological profiles. To further validate our findings, the molecular reactivity and stability were computed using the DFT calculation and molecular dynamics simulation, providing a deeper understanding of the stability and behavior of the top-ranking compounds in a biological environment. The outcomes of our study identified a subset of natural compounds that, based on our analysis, demonstrate notable potential as antifungal candidates. With further experimental validation, these compounds could pave the way for new therapeutic strategies against drug-resistant fungal pathogens.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":" 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141677552","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}
Jéssica da Silva Sena, Selma Alves Rodrigues, Karina Sakumoto, Rodrigo Sadao Inumaro, Pamela González-Maldonado, Emilio Mendez-Scolari, Ranulfo Piau, D. D. Gonçalves, Filipa Mandim, Josiana Vaz, José Eduardo Gonçalves, P. Sotelo, J. S. Valle, Z. C. Gazim
The chemical composition of extracts (CEs) and essential oils (EOs) from Tetradenia riparia leaves, flower buds, and stems was analyzed. Antiproliferative activity against tumor cell lines, NO production inhibition, and antioxidant and antiviral activities were assessed. The CEs contained flavonoids, phenolic acids, coumarins, and saturated fatty acids. The EOs included monoterpenes, oxygenated sesquiterpenes, and diterpenes. NO production inhibition ranged from 76 to 247 µg mL−1, and antiproliferative activity exhibited GI50 between 20 and >204 µg mL−1, with low cytotoxicity (SI: 1.08 to 4.75). Reactive oxygen species inhibition ranged from 45 to 82%. Antioxidant activity varied when determined by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (IC50: 0.51 to 8.47 mg mL−1) and ferric reducing antioxidant power (0.35 to 0.81 µM ferrous sulfate per mg). The reduction in β-carotene–linoleic acid co-oxidation varied between 76.13 and 102.25%. The total phenolic content of CEs and EOs was 10.70 to 111.68 µg gallic acid mg−1. Antiviral activity against herpes simplex virus type 1 (HSV-1) showed an EC50 between 9.64 and 24.55 µg mL−1 and an SI between 8.67 and 15.04. Leaf EOs exhibited an EC50 of 9.64 µg mL−1 and an SI of 15.04. Our study unveils the diverse chemical composition and multifaceted pharmacological properties of T. riparia, demonstrating its potential as a valuable source of bioactive compounds for therapeutic applications.
{"title":"Antioxidant Activity, Antiproliferative Activity, Antiviral Activity, NO Production Inhibition, and Chemical Composition of Essential Oils and Crude Extracts of Leaves, Flower Buds, and Stems of Tetradenia riparia","authors":"Jéssica da Silva Sena, Selma Alves Rodrigues, Karina Sakumoto, Rodrigo Sadao Inumaro, Pamela González-Maldonado, Emilio Mendez-Scolari, Ranulfo Piau, D. D. Gonçalves, Filipa Mandim, Josiana Vaz, José Eduardo Gonçalves, P. Sotelo, J. S. Valle, Z. C. Gazim","doi":"10.3390/ph17070888","DOIUrl":"https://doi.org/10.3390/ph17070888","url":null,"abstract":"The chemical composition of extracts (CEs) and essential oils (EOs) from Tetradenia riparia leaves, flower buds, and stems was analyzed. Antiproliferative activity against tumor cell lines, NO production inhibition, and antioxidant and antiviral activities were assessed. The CEs contained flavonoids, phenolic acids, coumarins, and saturated fatty acids. The EOs included monoterpenes, oxygenated sesquiterpenes, and diterpenes. NO production inhibition ranged from 76 to 247 µg mL−1, and antiproliferative activity exhibited GI50 between 20 and >204 µg mL−1, with low cytotoxicity (SI: 1.08 to 4.75). Reactive oxygen species inhibition ranged from 45 to 82%. Antioxidant activity varied when determined by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (IC50: 0.51 to 8.47 mg mL−1) and ferric reducing antioxidant power (0.35 to 0.81 µM ferrous sulfate per mg). The reduction in β-carotene–linoleic acid co-oxidation varied between 76.13 and 102.25%. The total phenolic content of CEs and EOs was 10.70 to 111.68 µg gallic acid mg−1. Antiviral activity against herpes simplex virus type 1 (HSV-1) showed an EC50 between 9.64 and 24.55 µg mL−1 and an SI between 8.67 and 15.04. Leaf EOs exhibited an EC50 of 9.64 µg mL−1 and an SI of 15.04. Our study unveils the diverse chemical composition and multifaceted pharmacological properties of T. riparia, demonstrating its potential as a valuable source of bioactive compounds for therapeutic applications.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":" 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141678024","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}
Hanem F. El-Gendy, A. El-Bahrawy, Doaa A. Mansour, Nagwa I. Sheraiba, Nazema S. Abdel-Megeid, S. Selim, R. Alhotan, Anam Ayyoub, Saber El Hanbally
5-Fluorouracil (5-FU) is often used as a chemotherapeutic agent in treating tumors and is said to have adverse effects, including nephrotoxicity. Therefore, the present study aimed to evaluate the protective effects of Chlorella vulgaris (VL) and Saccharum officinarum L. (SOL) against 5-FU-induced nephrotoxicity in rats through the measurement of renal histology, kidney damage indicators, and antioxidant measures. A total of forty-eight male rats were allotted into six groups: group 1 acted as a control negative group (control), group 2 received 5-FU and worked as a control positive group (FU), group 3 received SOL 15 mL/kg (SOL), group 4 received VL 400 mg/kg (VL), group 5 received 5-FU+SOL (5-FU+SOL), and group 6 received 5-FU+VL (5-FU+VL). After fifteen days, blood and renal tissue specimens were collected for hematological, biochemical, molecular, and histopathological examinations. Findings of the current investigation showed that 5-FU leads to hematological alterations and kidney injury evinced by elevated serum concentrations of uric acid, creatinine, and urea (p < 0.01), and a marked increase in kidney MDA and NO levels with a reduction in kidney CAT, SOD and GSH activities (p < 0.05). Alterations of the histopathological structure of kidney tissue in the FU group were noticed compared to the other groups. 5-FU administration elevated expression levels of TNF-α, lipocalin 2, and KIM1 (p < 0.01) compared to the control ones. 5-FU-induced nephrotoxicity was ameliorated after treatment with SOL and VL via their free radical scavenging, potent antioxidant, and anti-inflammatory effects. In conclusion, our findings demonstrate that the treatment with SOL and VL significantly improved nephrotoxicity induced by 5-FU in rats.
{"title":"Unraveling the Potential of Saccharum officinarum and Chlorella vulgaris towards 5-Fluorouracil-Induced Nephrotoxicity in Rats","authors":"Hanem F. El-Gendy, A. El-Bahrawy, Doaa A. Mansour, Nagwa I. Sheraiba, Nazema S. Abdel-Megeid, S. Selim, R. Alhotan, Anam Ayyoub, Saber El Hanbally","doi":"10.3390/ph17070885","DOIUrl":"https://doi.org/10.3390/ph17070885","url":null,"abstract":"5-Fluorouracil (5-FU) is often used as a chemotherapeutic agent in treating tumors and is said to have adverse effects, including nephrotoxicity. Therefore, the present study aimed to evaluate the protective effects of Chlorella vulgaris (VL) and Saccharum officinarum L. (SOL) against 5-FU-induced nephrotoxicity in rats through the measurement of renal histology, kidney damage indicators, and antioxidant measures. A total of forty-eight male rats were allotted into six groups: group 1 acted as a control negative group (control), group 2 received 5-FU and worked as a control positive group (FU), group 3 received SOL 15 mL/kg (SOL), group 4 received VL 400 mg/kg (VL), group 5 received 5-FU+SOL (5-FU+SOL), and group 6 received 5-FU+VL (5-FU+VL). After fifteen days, blood and renal tissue specimens were collected for hematological, biochemical, molecular, and histopathological examinations. Findings of the current investigation showed that 5-FU leads to hematological alterations and kidney injury evinced by elevated serum concentrations of uric acid, creatinine, and urea (p < 0.01), and a marked increase in kidney MDA and NO levels with a reduction in kidney CAT, SOD and GSH activities (p < 0.05). Alterations of the histopathological structure of kidney tissue in the FU group were noticed compared to the other groups. 5-FU administration elevated expression levels of TNF-α, lipocalin 2, and KIM1 (p < 0.01) compared to the control ones. 5-FU-induced nephrotoxicity was ameliorated after treatment with SOL and VL via their free radical scavenging, potent antioxidant, and anti-inflammatory effects. In conclusion, our findings demonstrate that the treatment with SOL and VL significantly improved nephrotoxicity induced by 5-FU in rats.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":" 48","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141679171","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}
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