Exploration of drug science最新文献

Enhanced breast cancer cell targeting: RGD integrin ligand potentiates RWQWRWQWR’s cytotoxicity and inhibits migration 增强乳腺癌细胞靶向性：RGD 整合素配体可增强 RWQWRWQWR 的细胞毒性并抑制迁移

Exploration of drug science Pub Date : 2024-07-19 DOI: 10.37349/eds.2024.00052

A. Barragán-Cárdenas, Daniel Castellar-Almonacid, Yerly Vargas-Casanova, C. Parra-Giraldo, Adriana Umaña-Pérez, J. López-Meza, Z. Rivera-Monroy, J. García-Castañeda

{"title":"Enhanced breast cancer cell targeting: RGD integrin ligand potentiates RWQWRWQWR’s cytotoxicity and inhibits migration","authors":"A. Barragán-Cárdenas, Daniel Castellar-Almonacid, Yerly Vargas-Casanova, C. Parra-Giraldo, Adriana Umaña-Pérez, J. López-Meza, Z. Rivera-Monroy, J. García-Castañeda","doi":"10.37349/eds.2024.00052","DOIUrl":"https://doi.org/10.37349/eds.2024.00052","url":null,"abstract":"Aim: Evaluate the selective cytotoxic effect of the palindromic sequence RWQWRWQWR and its analogues obtained by replacement of L-amino acids by D-amino acids or the functionalization by adding the RGD (integrin ligand motif) to the peptide. Methods: Peptides were obtained by SPPS, characterized by RP-HPLC and ESI-QTOF and its biological activity was evaluated using MTT assays. Evaluation of mechanism associated to the cytotoxic effect were carried out by flow cytometry, RT-qPCR, wound healing, transwell and zymography. Results: The peptides with replacements of D-amino acid showed a lesser cytotoxic effect against breast cancer cell lines, regardless it was one or several residues modified which suggested a possible specific interaction between the peptide and the cancer cell membrane besides its initial electrostatically contact. On the other hand, addition of the RGD sequence to the palindromic peptide in the N-terminal end resulted in a greater cytotoxic effect against cell lines derived from the three mainly diagnosed breast cancer molecular subtypes. An approximation on mechanisms associated to this effect was evaluated on MCF-7 cells, it shows that the peptide induced apoptosis by activating intrinsic and extrinsic pathway, which correlates with the possibility of a specific interaction, and induces mitochondrial depolarization with release of oxygen reactive species. Also, this peptide induces a reduction in migration and invasion associated with a diminish in metalloprotease 9 activity and a lesser release of IL-6, IL-10 and arginase cytokines. Conclusions: Our results suggest that this promising peptide can be considered for preclinical evaluation in the development of drugs to treat breast cancer and thus mitigate the impact of this disease.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":" 365","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141823599","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

Plants and fungi metabolites as novel autophagy inducers and senescence inhibitors 作为新型自噬诱导剂和衰老抑制剂的植物和真菌代谢物

Exploration of drug science Pub Date : 2024-07-01 DOI: 10.37349/eds.2024.00051

Rivka Ofir

{"title":"Plants and fungi metabolites as novel autophagy inducers and senescence inhibitors","authors":"Rivka Ofir","doi":"10.37349/eds.2024.00051","DOIUrl":"https://doi.org/10.37349/eds.2024.00051","url":null,"abstract":"Premature aging can be partially explained by inefficient autophagy (the process of cellular self-digestion that recycles intracellular components) and premature senescence (cease of cellular division without cell death activation). Autophagy and senescence are among the basic biochemical pathways in plants and fungi suggesting that some of their metabolites have the potential to act as autophagy inducers (AI) and senescence inhibitors (SI) and to inhibit inflammation and human aging. Several compounds have already been identified: trehalose and resveratrol are natural compounds that act as AI; flavonoids found in fruit and vegetables (curcumin, quercetin, and fisetin) are among the first SI discovered so far. New AI/SI can be identified using various approaches like hypothesis-driven approach for screening receptor agonists using an in-silico library of thousands of natural compounds; cheminformatics studies of phytochemicals using docking and molecular dynamics simulation, structure similarities/mimicry in vitro, “blind” high throughput screening (HTS) of libraries of natural metabolites against relevant models, and more. This article aims to promote the use of plant and fungi novel resources to identify bioactive molecules relevant for healthy aging based on the knowledge that plants and fungi use autophagy and senescence mechanisms for their own survival and homeostasis. As autophagy and senescence are interconnected, how drugs targeting autophagy, senescence, or both could contribute to healthy aging in humans will be speculated.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"10 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141703566","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

Interaction of norsecurinine-type monomeric and dimeric alkaloids with α-tubulin: a molecular docking study 去甲苏氨酸类单体生物碱和二聚生物碱与α-微管蛋白的相互作用：分子对接研究

Exploration of drug science Pub Date : 2024-05-21 DOI: 10.37349/eds.2024.00047

Gérard Vergoten, Christian Bailly

{"title":"Interaction of norsecurinine-type monomeric and dimeric alkaloids with α-tubulin: a molecular docking study","authors":"Gérard Vergoten, Christian Bailly","doi":"10.37349/eds.2024.00047","DOIUrl":"https://doi.org/10.37349/eds.2024.00047","url":null,"abstract":"Aim: New microtubule-targeting agents are needed to improve cancer treatment. The recent characterization of the anticancer alkaloid securinine as a tubulin-binding agent prompted us to explore the interaction of related monomeric and dimeric analogues with tubulin. The interaction between the α/β-tubulin dimer and alkaloids fluevirines A–F and flueggenines A–I, isolated from the bush Flueggea virosa (Roxb. ex Willd.) Royle, was investigated using molecular docking. Methods: Two molecular models were initially compared for the binding of securinine to α/β-tubulin. The pironetin-binding site model (5FNV) was selected for the subsequent docking analysis with all compounds. Empirical energies of interaction (ΔE) were measured and compared. Results: Fluevirine A has been identified as a potent tubulin binder. This dimeric alkaloid formed more stable complexes with tubulin than the monomeric counterparts, such as fluevirines B–D. The bis-indole derivative fluevirine E also provided more stable complexes than (nor)securinine. The study was extended to the dimeric alkaloids flueggenines A–I and three compounds were identified as potential tubulin binders: the polycyclic product flueggenine B, the norsecurinine-indole hybrid flueggenine E, and the norsecurinine dimer flueggenine I. This later compound proved to be well adapted to fit into the pironetin site of tubulin, extending its two norsecurinine units between the colchicine-binding area and the pironetin site, in close proximity to the pironetin-reactive cysteine-316 residue. Structure-binding relationships were delineated. Conclusions: The study identifies the dimeric alkaloids fluevirine A and flueggenine I as potential α-tubulin binding agents. For the first time, dimeric alkaloids including two C-C connected norsecurinine units are characterized as tubulin ligands. The study contributes to a better understanding of the mechanism of action of Flueggea alkaloids and should help the design of anticancer analogues targeting the pironetin site of α-tubulin.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"131 38","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141115055","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: 1

Pain management for the neurosurgical patient in spinal procedures: overview of historic and new modalities 脊柱手术中神经外科患者的疼痛管理：历史和新模式概述

Exploration of drug science Pub Date : 2024-05-21 DOI: 10.37349/eds.2024.00046

Ashley M. Carter, Samantha Yost, Jessica Tobin, Simran Phuyal, Brandon Lucke-Wold

引用次数: 0

Stryphnodendron adstringens have a modulatory effect on inflammatory cytokines markers of in vitro activated macrophages Stryphnodendron adstringens 对体外活化巨噬细胞的炎症细胞因子标记有调节作用

Exploration of drug science Pub Date : 2024-05-11 DOI: 10.37349/eds.2024.00045

I. D. da Cruz, C. F. Teixeira, N. L. Pellenz, M. Mastella, V. Azzolin, Euler Esteves Ribeiro, F. Barbisan

{"title":"Stryphnodendron adstringens have a modulatory effect on inflammatory cytokines markers of in vitro activated macrophages","authors":"I. D. da Cruz, C. F. Teixeira, N. L. Pellenz, M. Mastella, V. Azzolin, Euler Esteves Ribeiro, F. Barbisan","doi":"10.37349/eds.2024.00045","DOIUrl":"https://doi.org/10.37349/eds.2024.00045","url":null,"abstract":"Aim: The purpose of this study is to conduct a comprehensive investigation into the modulatory effects of Stryphnodendron adstringens (Mart.; S. adstringens), a Brazilian wound-healing plant, on the expression of inflammatory cytokines. This will be achieved using an in vitro protocol with the commercial macrophage cell line RAW 264.7. Methods: The macrophage inflammatory response was induced by the natural antigen phytohemagglutinin (PHA), with and without supplementation of different concentrations of S. adstringens extract. The effects on cell proliferation rate and the concentration and production of transcripts of pro-inflammatory cytokines interleukin 1β (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), as well as the anti-inflammatory cytokine IL-10, were assessed using spectrophotometric, immunoassay, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) techniques. Results: S. adstringens extract at all concentrations tested here reduced the cellular proliferation rate of activated macrophages. Extracts at concentrations of 0.49 mg/mL and 0.99 mg/mL decreased the protein and gene expression of pro-inflammatory cytokines, exhibiting the opposite effect concerning IL-10. Conclusions: The findings suggest that the wound-healing action of S. adstringens may encompass differential modulation of inflammation associated with tissue injury.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"117 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140987797","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

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