Exploration of drug science最新文献_第2页

Subacute toxicity of isoliquiritigenin-zein phosphatidylcholine nanoparticles on biochemical, hematological, and histopathological parameters in Sprague-Dawley rats 异尿素-玉米蛋白磷脂酰胆碱纳米颗粒对Sprague-Dawley大鼠生化、血液学和组织病理学参数的亚急性毒性

Exploration of drug science Pub Date : 2024-04-29 DOI: 10.37349/eds.2024.00044

Ke Yang, Kumar Ganesan, Fei Gao, Chunguang Xie, Jianping Chen

{"title":"Subacute toxicity of isoliquiritigenin-zein phosphatidylcholine nanoparticles on biochemical, hematological, and histopathological parameters in Sprague-Dawley rats","authors":"Ke Yang, Kumar Ganesan, Fei Gao, Chunguang Xie, Jianping Chen","doi":"10.37349/eds.2024.00044","DOIUrl":"https://doi.org/10.37349/eds.2024.00044","url":null,"abstract":"Aim: Isoliquiritigenin (ISL) is a natural flavonoid found in many natural plants, which exhibits numerous pharmacological properties including anti-inflammatory, antioxidant, antitumor, and antiviral activities. However, the low bioavailability and stability of ISL limit its application in clinical practice. To overcome these limitations, ISL-zein phosphatidylcholine hybrid nanoparticles (ISL@ZLH NPs) have been developed to improve the bioavailability and stability of ISL. The present study aimed to evaluate the acute and subacute toxicity of ISL@ZLH NPs in Sprague-Dawley (SD) rats. Methods: The ISL@ZLH NPs were prepared by the solvent evaporation method. The acute toxicity was evaluated by administering a single dose of 110 mg/kg and 160 mg/kg of ISL@ZLH NPs extracted in distilled water via oral gavage in rats and mice, respectively. The subacute toxicity was evaluated by administering doses of 27.5 mg/(kg∙day), 55 mg/(kg∙day), and 110 mg/(kg∙day) of ISL@ZLH NPs for 30 days and 90 days. The biochemical, hematological, and histopathological parameters were analyzed in both studies. Results: In the acute toxicity study, no mortality or significant changes in the biochemical and hematological parameters were observed in both Kunming (KM) mice and SD rats. In the subacute toxicity study, no toxic reactions were observed in both species at all doses tested. Moreover, no significant changes in the biochemical, hematological and histopathological parameters were observed in both species. Conclusions: The results of this study suggest that ISL@ZLH NPs are safe and non-toxic in both KM mice and SD rats. The nanoparticles (NPs) did not induce any adverse effects on the biochemical, hematological, and histopathological parameters in both acute and subacute toxicity studies. These results indicate that ISL@ZLH NPs are safe for prolonged consumption. Further studies are needed to evaluate the long-term toxicity and efficacy of these NPs in vivo.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"1 1","pages":"234-253"},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147909062","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: 5

Daropeptide natural products 达罗肽天然产品

Exploration of drug science Pub Date : 2024-04-19 DOI: 10.37349/eds.2024.00042

Suze Ma, Sijia Guo, Wei Ding, Qi Zhang

引用次数: 0

Stapled peptides: targeting protein-protein interactions in drug development 带钉肽：在药物开发中瞄准蛋白质与蛋白质之间的相互作用

Exploration of drug science Pub Date : 2024-04-18 DOI: 10.37349/eds.2024.00041

Qian Zhang, Ziyang Wang, Xiaohan Mei, Quan Chen, Chunqiu Zhang

引用次数: 0

Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives 旨在延缓或逆转正常衰老过程的药物和生物制剂临床研究--新成果和未来展望

Exploration of drug science Pub Date : 2024-04-10 DOI: 10.37349/eds.2024.00040

Ricardo P. Garay

{"title":"Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives","authors":"Ricardo P. Garay","doi":"10.37349/eds.2024.00040","DOIUrl":"https://doi.org/10.37349/eds.2024.00040","url":null,"abstract":"Five families of investigational products are in clinical investigation to slow or reverse normal aging processes [longevity candidates, mesenchymal stem cells, senolytics drugs, sirtuin activators, and nicotinamide adenine dinucleotide (NAD)+ precursors]. The longevity candidates, vitamin D and metformin, appear to significantly reduce all-cause mortality and prolong life expectancy. This should be confirmed by interventional studies. The mesenchymal stem cell family is the most advanced in clinical trial development [phase 2b randomized controlled trial (RCT)]. An allogeneic bone marrow stem cell preparation (Lomecel-B) reduced locomotor frailty in older people. The improvement in locomotion was modest. In the future, attempts could be made to improve potency through a precondition or genetic modification of naive bone marrow stem cells. Autologous adipose stem cell-assisted fat grafting increased graft survival, facial volume, and skin quality. The association of the senolytic drugs dasatinib and quercetin was well tolerated, with low brain penetration of dasatinib and undetectable levels of quercetin. The sirtuin-1 activator resveratrol (combined with physical exercise) improved physical function in older adults with physical limitations. The NAD+ precursor nicotinamide riboside improved physical exercise performance. In conclusion, Lomecel-B is the most advanced agent in clinical trial development for normal aging processes (phase 2b for locomotion frailty), followed by resveratrol and nicotinamide riboside.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140716697","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

Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonists for the treatment of obesity and diabetes mellitus 治疗肥胖症和糖尿病的胰高血糖素样肽-1 和葡萄糖依赖性促胰岛素多肽激动剂

Exploration of drug science Pub Date : 2024-04-03 DOI: 10.37349/eds.2024.00039

Alexander C Martins, B. G. de la Torre, Fernando Albericio

{"title":"Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonists for the treatment of obesity and diabetes mellitus","authors":"Alexander C Martins, B. G. de la Torre, Fernando Albericio","doi":"10.37349/eds.2024.00039","DOIUrl":"https://doi.org/10.37349/eds.2024.00039","url":null,"abstract":"Pharmaceutical interventions play a vital role in managing various conditions, including weight-related issues such as obesity. In this context, lifestyle changes are often challenging to maintain, especially for individuals struggling with this condition. Obesity is strongly linked to serious health conditions like cardiovascular disease and insulin resistance, leading to a cascade of health risks. Importantly, the development of effective and safe weight loss medications has been challenging. Diabetes mellitus (DM), the incidence of which is also rising, is closely related to obesity. The annual rate of DM cases has increased significantly, mirroring trends in obesity. Pharmaceutical companies have made significant progress in developing drugs that address both diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a promising class of medications with dual benefits in managing diabetes and aiding weight loss such as semaglutide, liraglutide, dulaglutide, exenatide, among others. However, despite their effectiveness, they can be expensive. The availability of various GLP-1RAs offers flexibility in diabetes management, but the surge in their prescription has led to a global shortage. Health authorities are working to address this issue, while pharmaceutical companies are exploring new paths to improve the quality of these drugs. In this context, tirzepatide stands out as a medication targeting key hormones involved in obesity and DM. Another potential breakthrough, retatrutide, is also being developed for these two conditions, but it requires further research. In this paper, the authors address all the GLP-1RA options developed to date, covering their mechanisms of action, efficacy, and chemical structures, among other aspects.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"24 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140746285","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

Mini-review on the antimicrobial potential of actinobacteria associated with seagrasses 与海草有关的放线菌抗菌潜力小综述

Exploration of drug science Pub Date : 2024-02-29 DOI: 10.37349/eds.2024.00038

Galana Siro, Atanas Pipite

{"title":"Mini-review on the antimicrobial potential of actinobacteria associated with seagrasses","authors":"Galana Siro, Atanas Pipite","doi":"10.37349/eds.2024.00038","DOIUrl":"https://doi.org/10.37349/eds.2024.00038","url":null,"abstract":"The search for novel therapeutic agents to combat the crisis of antimicrobial resistance has spanned from terrestrial to unique, marine environments. Currently, most of the drugs available for usage are derived from microbial metabolites, especially those belonging to the bacterial group, actinobacteria. Actinobacteria are hotspot organisms that exist in all habitats with a myriad of unique biosynthetic metabolites. Seagrasses appear to be a key ecosystem within the coastal environment worth bioprospecting for novel natural products. Unfortunately, literature about the bioactive potential of their associated prokaryotes, including actinobacteria remains limited. In this context, this review focused on actinobacteria with antibiotic-producing capabilities derived from different parts of seagrass plants (i.e. roots, rhizomes, and leaves). To date, there were no purified molecules derived from seagrass-associated actinobacteria that were subjected to structure elucidation. From the underpinning of numerous biological profiles such as antibacterial, antifungal, and algicidal activities of seagrass-derived actinobacteria reported in this review during the period from 2012–2020, it provides a continual growth of knowledge accruing overtime, providing a foundation for future research.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140414831","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

Influenza A virus hemagglutinin: from classical fusion inhibitors to proteolysis targeting chimera-based strategies in antiviral drug discovery 甲型流感病毒血凝素：从经典的融合抑制剂到基于蛋白水解靶向嵌合体的抗病毒药物研发策略

Exploration of drug science Pub Date : 2024-02-29 DOI: 10.37349/eds.2024.00037

Francisco Javier Hermoso-Pinilla, Aitor Valdivia, M. Camarasa, Tiziana Ginex, F. J. Luque

{"title":"Influenza A virus hemagglutinin: from classical fusion inhibitors to proteolysis targeting chimera-based strategies in antiviral drug discovery","authors":"Francisco Javier Hermoso-Pinilla, Aitor Valdivia, M. Camarasa, Tiziana Ginex, F. J. Luque","doi":"10.37349/eds.2024.00037","DOIUrl":"https://doi.org/10.37349/eds.2024.00037","url":null,"abstract":"The influenza virus glycoprotein hemagglutinin (HA) participates in critical steps of the attachment of viral particles to the host cell membrane receptor and membrane fusion. Due to its crucial involvement in the initial phases of influenza A infections, HA emerges as a promising target in the search of novel drug-like candidates. Given its pivotal role in the early stages of influenza A infections, intense drug discovery efforts have been undertaken to target HA in the past decades. Drug discovery studies mainly rely on preventing the recognition of sialic acid units by the receptor binding site in the globular head (GH) domain, or the conformational rearrangement required for the fusion of viral and cell membranes. In this work, the aim is to summarize the progress made in HA-targeted development of small molecule fusion inhibitors. To this end, attention will primarily be focused on the analysis of the X-ray crystallographic structures of HA bound to fusion inhibitors. Furthermore, this study also aims to highlight the efforts made in exploiting the structural information in conjunction with molecular modeling techniques to discern the mechanism of action of the fusion inhibitors and to assist the design and interpretation of structure-activity relationships of novel lead compounds will be highlighted. The final section will be dedicated to elucidating novel and promising antiviral strategies proceeding from the transformation of known small molecule antivirals in proteolysis targeting chimera (PROTAC)-based targeted protein degradation. This knowledge will be valuable to assist the exploitation of classical and novel antiviral structure-based strategies, together with a deeper understanding of the mechanism of action and minimization of the impact of drug resistance.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"9 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140414496","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

Effect of the size of nucleic acid delivery systems on their fate in cancer treatment 核酸递送系统的大小对其在癌症治疗中的命运的影响

Exploration of drug science Pub Date : 2024-02-01 DOI: 10.37349/eds.2024.00035

Mengyun Ye, Junni Gong, Wang Chen, Xiaoxuan Liu, Da-Ni Zhu

{"title":"Effect of the size of nucleic acid delivery systems on their fate in cancer treatment","authors":"Mengyun Ye, Junni Gong, Wang Chen, Xiaoxuan Liu, Da-Ni Zhu","doi":"10.37349/eds.2024.00035","DOIUrl":"https://doi.org/10.37349/eds.2024.00035","url":null,"abstract":"Nucleic acid therapeutics are emerging as a promising class of medicines, offering unique therapeutic options for cancer at the gene level. However, the druggability of nucleic acid therapeutics is fundamentally restricted by their low stability, poor membrane permeability, and low bioavailability, necessitating the use of delivery vectors. Various delivery vectors have been developed for nucleic acid therapeutics. The fate of established nucleic acid delivery systems (NADS) in vivo substantially affects the delivery efficiency and therapeutic efficacy. The physicochemical properties of NADS (such as size, charge, shape, etc) are crucial for the interaction of NADS with various biological barriers in the body, thereby determining the fate of NADS in the body. Nanoparticle (NP) size is an important parameter defining the blood circulation, distribution, tumor accumulation, and cellular uptake of NADS. This mini-review briefly introduces the various biological barriers of NADS in cancer treatment and focuses on the influence of the particle size of delivery vectors on the in vivo fate of NADS and their therapeutic efficacy, which provides new insights into the rational design of NADS.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"58 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139817378","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

Revisiting 310-helices: biological relevance, mimetics and applications 重新审视 310-螺旋：生物学意义、仿生学和应用

Exploration of drug science Pub Date : 2024-02-01 DOI: 10.37349/eds.2024.00034

Diego Núñez-Villanueva

{"title":"Revisiting 310-helices: biological relevance, mimetics and applications","authors":"Diego Núñez-Villanueva","doi":"10.37349/eds.2024.00034","DOIUrl":"https://doi.org/10.37349/eds.2024.00034","url":null,"abstract":"310-Helices represent the third most abundant secondary structure proteins. Although understandably overshadowed by α-helices for decades, the 310-helix structure is slowly regaining certain relevance in protein science. The key role of this secondary structure in biological processes has been highlighted in reports over the last decade. In addition, 310-helices are considered key intermediates in protein folding as well as a crucial structure for the antimicrobial activity of naturally occurring peptaibols. Thus, it is clear that 310-helices are relevant scaffolds to take into consideration in the field of biomimetics. In this context, this review covers the strategies developed to stabilize the 310-helix structure in peptide chains, from the incorporation of constrained amino acids to stapling methodologies. In the last section, the use of 310-helices as scaffolds of interest in the development of bioactive compounds, catalysts for enantioselective reactions, supramolecular receptors, and membrane-embedded signal transducers are discussed. The present work aims to highlight the relevance, sometimes underestimated, of 310-helices in chemical biology and protein science, providing the tools to develop functional biomimetics with a wide range of potential applications.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"52 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139687117","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

Effect of the size of nucleic acid delivery systems on their fate in cancer treatment 核酸递送系统的大小对其在癌症治疗中的命运的影响

Exploration of drug science Pub Date : 2024-02-01 DOI: 10.37349/eds.2024.00035

Mengyun Ye, Junni Gong, Wang Chen, Xiaoxuan Liu, Da-Ni Zhu

{"title":"Effect of the size of nucleic acid delivery systems on their fate in cancer treatment","authors":"Mengyun Ye, Junni Gong, Wang Chen, Xiaoxuan Liu, Da-Ni Zhu","doi":"10.37349/eds.2024.00035","DOIUrl":"https://doi.org/10.37349/eds.2024.00035","url":null,"abstract":"Nucleic acid therapeutics are emerging as a promising class of medicines, offering unique therapeutic options for cancer at the gene level. However, the druggability of nucleic acid therapeutics is fundamentally restricted by their low stability, poor membrane permeability, and low bioavailability, necessitating the use of delivery vectors. Various delivery vectors have been developed for nucleic acid therapeutics. The fate of established nucleic acid delivery systems (NADS) in vivo substantially affects the delivery efficiency and therapeutic efficacy. The physicochemical properties of NADS (such as size, charge, shape, etc) are crucial for the interaction of NADS with various biological barriers in the body, thereby determining the fate of NADS in the body. Nanoparticle (NP) size is an important parameter defining the blood circulation, distribution, tumor accumulation, and cellular uptake of NADS. This mini-review briefly introduces the various biological barriers of NADS in cancer treatment and focuses on the influence of the particle size of delivery vectors on the in vivo fate of NADS and their therapeutic efficacy, which provides new insights into the rational design of NADS.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"173 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139877687","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