Biophysica最新文献_第5页

Exploring Quercetin Hydrate’s Potential as an Antiviral Treatment for Oropouche Virus 槲皮素水合物作为Oropouche病毒抗病毒治疗药物的潜力探索

Biophysica Pub Date : 2023-08-12 DOI: 10.3390/biophysica3030032

G. Menezes, M. Saivish, L. Sacchetto, G. C. D. da Silva, Igor da Silva Teixeira, Natalia Franco Bueno Mistrão, M. Nogueira, J. I. N. Oliveira, K. S. Bezerra, R. D. da Silva, U. L. Fulco

{"title":"Exploring Quercetin Hydrate’s Potential as an Antiviral Treatment for Oropouche Virus","authors":"G. Menezes, M. Saivish, L. Sacchetto, G. C. D. da Silva, Igor da Silva Teixeira, Natalia Franco Bueno Mistrão, M. Nogueira, J. I. N. Oliveira, K. S. Bezerra, R. D. da Silva, U. L. Fulco","doi":"10.3390/biophysica3030032","DOIUrl":"https://doi.org/10.3390/biophysica3030032","url":null,"abstract":"The Oropouche virus is an orthobunyavirus responsible for causing Oropouche fever, a disease that primarily affects thousands of people in South and Central America. Currently, no specific antiviral treatments or vaccines are available against this virus, highlighting the urgent need for safe, affordable, and effective therapies. Natural products serve as an important source of bioactive compounds, and there is growing interest in identifying natural bioactive molecules that could be used for treating viral diseases. Quercetin hydrate is a compound classified as a flavonoid, which has garnered scientific attention due to its potential health benefits and its presence in various plant-based foods. In this study, we aim to evaluate the in vitro antiviral activity of quercetin hydrate against the Oropouche virus (OROV). Furthermore, we intend to explore its mode of action through in silico approaches. The cytotoxicity and antiviral activity of the compound were assessed using Vero cells. In addition, in silico studies were also performed through molecular docking, molecular dynamics simulations, Molecular Mechanics Poisson–Boltzmann surface area (MM/PBSA), and quantum-mechanical analysis in order to evaluate the interaction with the Gc protein of OROV. The assay revealed that the compound was highly active against the virus, inhibiting OROV with an EC50 value of 53.5 ± 26.5 µM under post-infection treatment conditions. The present study demonstrates that the compound is a promising antiviral agent; however, the mechanisms of action proposed in this study need to be experimentally verified by future assays.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44810145","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

The Dynamic Behavior of a Single Semiflexible Ring Chain in a Linear Polymer Matrix 线性聚合物基体中单个半柔性环链的动力学行为

Biophysica Pub Date : 2023-07-26 DOI: 10.3390/biophysica3030031

Xiaolin Zhou, Yifan Qin

引用次数: 0

Exploring the Dynamics of Holo-Shikimate Kinase through Molecular Mechanics 用分子力学探讨全莽草激酶的动力学

Biophysica Pub Date : 2023-07-21 DOI: 10.3390/biophysica3030030

P. Ojeda-May

引用次数: 0

A Structure-Guided Designed Small Molecule Is an Anticancer Agent and Inhibits the Apoptosis-Related MCL-1 Protein 结构引导设计的小分子是一种抗癌剂并抑制凋亡相关的MCL-1蛋白

Biophysica Pub Date : 2023-07-07 DOI: 10.3390/biophysica3030029

Ingrid V. Machado, Luiz F. N. Naves, Jean M. F. Custódio, H. D. A. Vidal, J. E. Queiroz, A. Oliver, Joyce V. B. Borba, B. J. Neves, L. M. Brito, C. Pessoa, H. Napolitano, G. Aquino

{"title":"A Structure-Guided Designed Small Molecule Is an Anticancer Agent and Inhibits the Apoptosis-Related MCL-1 Protein","authors":"Ingrid V. Machado, Luiz F. N. Naves, Jean M. F. Custódio, H. D. A. Vidal, J. E. Queiroz, A. Oliver, Joyce V. B. Borba, B. J. Neves, L. M. Brito, C. Pessoa, H. Napolitano, G. Aquino","doi":"10.3390/biophysica3030029","DOIUrl":"https://doi.org/10.3390/biophysica3030029","url":null,"abstract":"Cancer resistance to chemotherapy and radiation therapies presents significant challenges, necessitating the exploration of alternative approaches. Targeting specific proteins at the molecular level, particularly their active sites, holds promise in addressing this issue. We investigated the potential of 4′-methoxy-2-nitrochalcone (MNC) as an MCL-1 inhibitor, examining its chemical and structural characteristics to elucidate its biological activity and guide the selection of potential candidates. We conducted a docking study, followed by synthesis, structural characterization, theoretical calculations, and in vitro experiments to comprehensively evaluate MNC. The docking results revealed MNC’s excellent binding within the active site of MCL-1. At 50 µM, MNC demonstrated 99% inhibition of HCT116 cell proliferation, with an IC50 value of 15.18 µM after 24 h. Treatment with MNC at 30.36 and 15.18 µM resulted in reduced cell density. Notably, MNC exhibited marked cytotoxicity at concentrations of 15.58 µM and 7.79 µM, inducing high frequencies of plasma membrane rupture and apoptosis, respectively. Our findings highlight the significant biological potential of MNC as an MCL-1 inhibitor. Furthermore, we propose exploring chalcones with hydrogen bond acceptor substituents as promising candidates for studying inhibitors targeting this protein. In conclusion, our study addresses the challenge of cancer resistance by investigating MNC as an MCL-1 inhibitor. Through detailed characterization and experimental validation, we establish the efficacof MNC in inhibiting cell proliferation and inducing cytotoxic effects. These results underscore the potential of MNC as a valuable therapeutic agent and suggest the use of chalcones with hydrogen bond acceptor substituents as a basis for developing novel MCL-1 inhibitors.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49073564","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

Screening for Bioactive Metabolites in Leaves, Branches, and Roots of Mansoa hirsuta: Phytochemical, Toxicological and Antioxidant Aspects Mansoa hirsuta叶、枝、根生物活性代谢物的筛选:植物化学、毒理学和抗氧化方面

Biophysica Pub Date : 2023-06-28 DOI: 10.3390/biophysica3030028

P. Alves, Gagan Preet, M. Oliveira, L. Dias, Giovanna B Silva, Maria Luísa Lima Barreto do Nascimento, A. Reis, João Marcelo Sousa, J. Júnior, N. Lima, T. Andrade, C. Feitosa

{"title":"Screening for Bioactive Metabolites in Leaves, Branches, and Roots of Mansoa hirsuta: Phytochemical, Toxicological and Antioxidant Aspects","authors":"P. Alves, Gagan Preet, M. Oliveira, L. Dias, Giovanna B Silva, Maria Luísa Lima Barreto do Nascimento, A. Reis, João Marcelo Sousa, J. Júnior, N. Lima, T. Andrade, C. Feitosa","doi":"10.3390/biophysica3030028","DOIUrl":"https://doi.org/10.3390/biophysica3030028","url":null,"abstract":"In this study, secondary metabolites, toxicology and antioxidant properties of chloroform fractions from leaves (FCFMh), branches (FCGMh), and roots (FCRMh) of Mansoa hirsuta were investigated. The phytochemical screening detected flavonoids, especially chalcones. Through Liquid chromatography with mass spectrometry—LC–MS analysis, the flavonoids (isoorientin-2″-O-arabinoside), triterpenes (oleanolic acid and ursolic acid) and ceramide (phytosphingosine) were identified. From the Artemia salina assay, the fraction FCGMh was the most toxic (LC50 = 64.21 µg·mL−1), followed by FCRMh (LC50 = 87.61 µg·mL−1) and FCFMh (LC50 = 421.9 µg·mL−1). Concerning the cytotoxic potential, the root fraction (IC50 16.48 μg mL−1) displayed the highest cytotoxicity against the breast cancer cell line (4T1), followed by leaves (IC50 33.13 μg mL−1) and branches (IC50 of 47.13 μg mL−1). In conclusion, all the fractions of M. hirsuta showed cytotoxicity at the highest concentrations; however, remarkable biological properties were found for the root fractions. Computational analysis was performed using a molecular docking and pharmacophore approach to understand the antioxidant activity of its major metabolites.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48590221","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

Adsorption of Heparin-Binding Fragments of Fibronectin onto Hydrophobic Surfaces 纤连蛋白肝素结合片段在疏水表面的吸附

Biophysica Pub Date : 2023-06-23 DOI: 10.3390/biophysica3030027

Viswanath Vittaladevaram, D. Cheung

引用次数: 0

A Two-Species Finite Volume Scalar Model for Modeling the Diffusion of Poly(lactic-co-glycolic acid) into a Coronary Arterial Wall from a Single Half-Embedded Drug Eluting Stent Strut 一个两种群有限体积标量模型用于模拟聚乳酸-乙醇酸从单个半嵌入式药物洗脱支架支架向冠状动脉壁的扩散

Biophysica Pub Date : 2023-06-15 DOI: 10.3390/biophysica3020026

Rodward L. Hewlin, Maegan Edwards, J. Kizito

{"title":"A Two-Species Finite Volume Scalar Model for Modeling the Diffusion of Poly(lactic-co-glycolic acid) into a Coronary Arterial Wall from a Single Half-Embedded Drug Eluting Stent Strut","authors":"Rodward L. Hewlin, Maegan Edwards, J. Kizito","doi":"10.3390/biophysica3020026","DOIUrl":"https://doi.org/10.3390/biophysica3020026","url":null,"abstract":"This paper outlines the methodology and results for a two-species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA)) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport model incorporates the convection-diffusion equation in scalar form (dimensionless) with a two-species (free-drug and bound-drug) mass transport setup, including reversible equilibrium reaction source terms for the free and bound-drug states to account for the pharmaco-kinetic reactions in the arterial wall. The relative reaction rates of the added source terms control the interconversion of the drug between the free and bound-drug states. The model is solved by a 2D finite-volume method for discretizing and solving the free and bound drug transport equations with anisotropic vascular drug diffusivities. This model is an improvement over previously developed models using the finite-difference and finite element method. A dimensionless characteristic scaling pre-analysis was conducted a priori to evaluate the significance of implementing the reaction source terms in the transport equations. This paper reports the findings of an investigation of the interstitial flow profile into the arterial wall and the free and bound drug diffusion profiles with a parametric study of varying the polymer drug concentration (low and high), tortuosity, porosity, and Peclet and DamKöhler numbers over the course of 400 h (16.67 days). The results also reveal how a single species drug delivery model that neglects both a reversible binding reaction source term and the porosity and tortuosity of the arterial wall cannot accurately predict the distribution of both the free and bound drug.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46356152","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

Computational Modeling of the Neurofibromin-Stimulated Guanosine Triphosphate Hydrolysis by the KRas Protein 神经纤维蛋白刺激鸟苷三磷酸KRas蛋白水解的计算模型

Biophysica Pub Date : 2023-05-31 DOI: 10.3390/biophysica3020025

I. Polyakov, A. Nemukhin

引用次数: 1

Decomposition of Small Molecules for Fragment-Based Drug Design 基于片段的药物设计中的小分子分解

Biophysica Pub Date : 2023-05-24 DOI: 10.3390/biophysica3020024

Nikita N. Ivanov, D. Shulga, V. Palyulin

引用次数: 0

Phenotypic and Biomechanical Characteristics of Human Fetal Neural Progenitor Cells Exposed to Pesticide Compounds 人类胚胎神经祖细胞暴露于农药的表型和生物力学特征

Biophysica Pub Date : 2023-05-18 DOI: 10.3390/biophysica3020023

Marissa C. Sarsfield, Jennifer Vasu, Sabreen M. Abuoun, N. Allena, C. Kothapalli

{"title":"Phenotypic and Biomechanical Characteristics of Human Fetal Neural Progenitor Cells Exposed to Pesticide Compounds","authors":"Marissa C. Sarsfield, Jennifer Vasu, Sabreen M. Abuoun, N. Allena, C. Kothapalli","doi":"10.3390/biophysica3020023","DOIUrl":"https://doi.org/10.3390/biophysica3020023","url":null,"abstract":"Various forms of pesticides have been reported to be among the environmental toxicants, which are detrimental to human health. The active ingredients of these formulations can enter the human body through air, food, or water. Epidemiological studies suggest that these compounds strongly affect the developing brain in fetal and infant stages due to their ability to breach the underdeveloped blood–brain barrier. Since neural progenitor stem cells (NPCs) in the developing brain are the most vulnerable to these compounds, the mechanisms by which NPCs experience toxicity upon exposure to these chemicals must be investigated. Here, we assessed the viability of human fetal NPCs in 2D cultures in the presence of the active ingredients of six widely used pesticides using Live/Dead® and Hoechst staining. The IC50 values ranged from 4.1–201 μM. A significant drop in cell viability with increasing toxicant concentration (p < 0.01) was noted, with the order of toxicity being malathion < 4-aminopyridine < methoprene < prallethrin < temephos < pyriproxyfen. Changes in cellular biomechanical characteristics (Young’s modulus, tether force, membrane tension, and tether radius) were quantified using atomic force microscopy, whereas cell migration was elucidated over 48 h using a customized wound-healing assay. The Young’s modulus of fetal NPCs exposed to IC50/2 doses of these compounds was reduced by 38–70% and that of those exposed to IC50 doses was reduced by 71–80% (p < 0.001 vs. controls for both; p < 0.01 for IC50 vs. IC50/2 for each compound). Similar patterns were noted for tether forces and membrane tension in fetal NPCs. NPC migration was found to be compound type- and dose-dependent. These results attest to the significant detrimental effects of these compounds on various aspects of the human fetal NPC phenotype, and the utility of cell mechanics as a marker to assess developmental neurotoxicity.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41473059","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