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排序方式: 共有444条查询结果,搜索用时 23 毫秒
1.
《Arabian Journal of Chemistry》2022,15(10):104145
In the present study, novel representatives of the important group of biologically-active, dehydroabietic acid-bearing dithiocarbamate moiety, were synthesized and characterized by 1H NMR, 13C NMR, HR-MS. The in vitro antiproliferative activity evaluation (MTT) indicated that these compounds exhibited potent inhibitory activities in various cancer cell lines (HepG-2, MCF-7, HeLa, T-24, MGC-803). Particularly, compound III-b possessed extraordinary cytotoxicity with low micromolar IC50 values ranging from 4.07 to 38.84 µM against tested cancer cell lines, while displayed weak cytotoxicity on two normal cell lines (LO-2 and HEK 293 T). Subsequently, the potential mechanisms of representative compound III-b were elementarily investigated by Transwell experiment, which showed III-b can inhibit cancer cells migration. Annexin-V/PI dual staining showed that the compound can induce HepG-2 cells apoptosis in a dose-dependent manner. Meanwhile this apoptosis may be related to the upregulated protein expression of cleaved-caspase 3, cleaved-caspase 9, Bax and downregulated of Bcl-2 indicated by Western Blot. Later study further confirmed that ROS levels in HepG-2 cells increased significantly with the rise of concentrations. In addition, through the network pharmacology data analyzing, the core targets and signaling pathways of compound III-b for treatment of liver neoplasms were forecasted. Molecular docking model showed that compound III-b had high affinity with hub targets (CASP3, EGFR, HSP90AA1, MAPK1, ERBB2, MDM2), suggesting that compound III-b might target the hub protein to modulate signaling activity. Taken together, these data indicated that dehydroabietic acid structural modification following the “Molecular hybridization” principle is a feasible way to discover the potential multi-targeted antitumor compounds. 相似文献
2.
In this paper, a periodic stochastic human immunodeficiency virus (HIV) model with distributed delay and cytotoxic T lymphocytes (CTL) immune response is investigated. First, by It 's formula, we show that the solution with any positive initial value is global and positive. Then, by the stochastic comparison theorem, we obtain the sufficient conditions guaranteeing the existence and global attractivity of infection-free periodic solution. Furthermore, we discuss the existence of the infective periodic solution by Has'minskii theory. Finally, numerical examples are given to illustrate the results. 相似文献
3.
4.
Ana R. M. Carvalho Carla M. A. Pinto 《Mathematical Methods in the Applied Sciences》2017,40(4):1231-1264
We study the contributions of within‐host (virus‐to‐cell) and synaptic (cell‐to‐cell) transmissions in a mathematical model for human immunodeficiency virus epidemics. The model also includes drug resistance. We prove the local and global stability of the disease‐free equilibrium and the local stability of the endemic equilibrium. We analyse the effect of the cell‐to‐cell transmission rate on the value of the reproduction number, R0. Moreover, we show evidence of a qualitative change in the models' dynamics, subjected to the value of the drug efficacy. In the end, important inferences are drawn. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
5.
《Macromolecular bioscience》2017,17(3)
The human immunodeficiency virus (HIV) continues to be a global pandemic and there is an urgent need for innovative treatment. Immune cells represent a major target of virus infection, but are also therapeutic targets. Currently, no antiretroviral therapy targets macrophages, which function as portal of entry and as major long‐term deposit of HIV. It has been shown before that human macrophages efficiently internalize gold nanoparticles, a fact which might be used to target them with drug‐nanoparticle conjugates. Here, the authors use gold nanocarriers to facilitate delivery of stavudine, a widely used antiretroviral drug, to primary human macrophages. Using an ease‐of‐use coupling method, a striking potentiation of stavudine intake by macrophages using gold nanocarriers is shown. Further, the carriers induce a specific subtype of proinflammatory activation indicative for antiviral activity of macrophages, which suggests promising novel treatment options for HIV.
6.
Recent studies demonstrate that resource competition is an essential component of T-cell proliferation in HIV progression, which can contribute instructively to the disease development. In this paper, we formulate an age-structured within-host HIV model, in the form of a hyperbolic partial differential equation (PDE) for infected target cells coupled with two ordinary differential equations for uninfected T-cells and the virions, to explore the effects of both the T-cell competition and viral shedding variations on the viral dynamics. The basic reproduction number is derived for a general viral production rate which determines the local stability of the infection-free equilibrium. Two special forms of viral production rates, which are extensively investigated in previous literature, the delayed exponential distribution and a step function rate, are further investigated, where the original system can be reduced into systems of delay differential equations. It is confirmed that there exists a unique positive equilibrium for two special viral production rates when the basic reproduction number is greater than one. However, the model exhibits the phenomenon of backward bifurcation, where two positive steady states coexist with the infection-free equilibrium when the basic reproduction number is less than one. 相似文献
7.
Tuniyazi Abuduaini Vincent Roy Julien Marlet Catherine Gaudy-Graffin Denys Brand Ccile Baronti Franck Touret Bruno Coutard Tamara R. McBrayer Raymond F. Schinazi Luigi A. Agrofoglio 《Molecules (Basel, Switzerland)》2021,26(5)
A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(E)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound 15j, a hexadecyloxypropyl (HDP)/(isopropyloxycarbonyl-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC50 = 66.4 μM in HepG2 cells, IC50 = 43.1 μM in HepG2 cells) at 10 μM. 相似文献
8.
Background: Thiazole is a good pharmacophore nucleus due to its various pharmaceutical applications. Its derivatives have a wide range of biological activities such as antioxidant, analgesic, and antimicrobial including antibacterial, antifungal, antimalarial, anticancer, antiallergic, antihypertensive, anti-inflammatory, and antipsychotic. Indeed, the thiazole scaffold is contained in more than 18 FDA-approved drugs as well as in numerous experimental drugs. Objective: To summarize recent literature on the biological activities of thiazole ring-containing compounds Methods: A literature survey regarding the topics from the year 2015 up to now was carried out. Older publications were not included, since they were previously analyzed in available peer reviews. Results: Nearly 124 research articles were found, critically analyzed, and arranged regarding the synthesis and biological activities of thiazoles derivatives in the last 5 years. 相似文献
9.
Antiviral Activity of Synthetic Aminopyrrolic Carbohydrate Binding Agents: Targeting the Glycans of Viral gp120 to Inhibit HIV Entry 下载免费PDF全文
Dr. Oscar Francesconi Prof. Cristina Nativi Dr. Gabriele Gabrielli Irene De Simone Sam Noppen Prof. Jan Balzarini Prof. Sandra Liekens Dr. Stefano Roelens 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(28):10089-10093
The binding abilities of a set of structurally related aminopyrrolic synthetic receptors for mannosides, endowed with antimycotic activity against yeast and yeast‐like pathogens bearing mannoproteins on their cell surface, have been investigated towards the highly mannosylated gp120 and gp41 glycoproteins of the HIV envelope. A pronounced binding interaction with both glycoproteins was observed by SPR for most of the investigated compounds. Comparison of their binding properties towards the glycoproteins with their binding affinities toward mannosides revealed a direct correlation, supporting their role as carbohydrate binding agents (CBAs). Cytostatic activity studies revealed antiproliferative activity dependent on the nature and the structure of compounds. Antiviral activity studies against a broad panel of DNA and RNA viruses showed inhibitory effect against HIV infection of the T‐lymphocyte CEM cell line for two compounds, suggesting antiviral activity similar to other CBAs, such as the nonpeptidic pradimicin antibiotics. 相似文献
10.
In this paper, applying both Lyapunov function techniques and monotone iterative techniques, we establish new sufficient conditions under which the infected equilibrium of an HIV pathogenesis model with cure rate is globally asymptotically stable. By giving an explicit expression for eventual lower bound of the concentration of susceptible CD4+ T cells, we establish an affirmative partial answer to the numerical simulations investigated in the recent paper [Liu, Wang, Hu and Ma, Global stability of an HIV pathogenesis model with cure rate, Nonlinear Analysis RWA (2011) 12 : 2947–2961]. Our monotone iterative techniques are applicable for the small and large growth rate in logistic functions for the proliferation rate of healthy and infected CD4+ T cells. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献