Search results for "AGENTS"
showing 10 items of 7330 documents
Reverse screening on indicaxanthin from Opuntia ficus-indica as natural chemoactive and chemopreventive agent
2018
Indicaxanthin is a bioactive and bioavailable betalain pigment extracted from Opuntia ficus indica fruits. Indicaxanthin has pharmacokinetic proprieties, rarely found in other phytochemicals, and it has been demonstrated that it provides a broad-spectrum of pharmaceutical activity, exerting anti-proliferative, anti-inflammatory, and neuromodulator effects. The discovery of the Indicaxanthin physiological targets plays an important role in understanding the biochemical mechanism. In this study, combined reverse pharmacophore mapping, reverse docking, and text-based database search identified Inositol Trisphosphate 3-Kinase (ITP3K-A), Glutamate carboxypeptidase II (GCPII), Leukotriene-A4 hydr…
Search of Chemical Scaffolds for Novel Antituberculosis Agents
2005
3 A method to identify chemical scaffolds potentially active against Mycobacterium tuberculosis is presented. The molecular features of a set of structurally heterogeneous antituberculosis drugs were coded by means of structural invariants. Three tech- niques were used to obtain equations able to model the antituberculosis activity: linear discriminant analysis, multilinear re- gression, and shrinkage estimation-ridge regression. The model obtained was statistically validated through leave-n-out test, and an external set and was applied to a database for the search of new active agents. The selected compounds were assayed in vitro, and among those identified as active stand reserpine, N,N,N…
Exploring Strategies for Labeling Viruses with Gold Nanoclusters through Non-equilibrium Molecular Dynamics Simulations.
2017
Biocompatible gold nanoclusters can be utilized as contrast agents in virus imaging. The labeling of viruses can be achieved noncovalently but site-specifically by linking the cluster to the hydrophobic pocket of a virus via a lipid-like pocket factor. We have estimated the binding affinities of three different pocket factors of echovirus 1 (EV1) in molecular dynamics simulations combined with non-equilibrium free-energy calculations. We have also studied the effects on binding affinities with a pocket factor linked to the Au102pMBA44 nanocluster in different protonation states. Although the absolute binding affinities are over-estimated for all the systems, the trend is in agreement with r…
Screening of potent phytochemical inhibitors against SARS-CoV-2 protease and its two Asian mutants
2021
Abstract Background COVID-19, declared a pandemic in March 2020 by the World Health Organization is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus has already killed more than 2.3 million people worldwide. Object The principal intent of this work was to investigate lead compounds by screening natural product library (NPASS) for possible treatment of COVID-19. Methods Pharmacophore features were used to screen a large database to get a small dataset for structure-based virtual screening of natural product compounds. In the structure-based screening, molecular docking was performed to find a potent inhibitor molecule against the main protease (Mpro) of SARS-…
Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine protease of Trypanosoma brucei
2016
A series of dipeptide nitriles known as inhibitors of mammalian cathepsins were evaluated for inhibition of rhodesain, the cathepsin L-like protease of Trypanosoma brucei. Compound 35 consisting of a Leu residue fitting into the S2 pocket and a triarylic moiety consisting of thiophene, a 1,2,4-oxadiazole and a phenyl ring fitting into the S3 pocket, and compound 33 with a 3-bromo-Phe residue (S2) and a biphenyl fragment (S3) were found to inhibit rhodesain in the single-digit nanomolar range. The observed steep structure-activity relationship could be explained by covalent docking simulations. With their high selectivity indices (ca. 200) and the good antitrypanosomal activity (8μM) the com…
Comparative study of the production of soluble factors in human placenta-derived mesenchymal stromal/stem cells grown in adherent conditions or as ag…
2019
Abstract Different approaches have been studied in both preclinical and clinical settings to develop cell-based therapies and/or engineered cell-based therapies to better integrate grafts with the host. In these techniques, much attention is addressed to the use of adult stem cells such as mesenchymal stem cells (MSCs), but identifying and obtaining sufficient numbers of therapeutic cells, and the right route of administration, is often a challenge. In this study, we tested the feasibility of encapsulating human amnion-derived MSCs (hAMSCs) in a semipermeable and biocompatible fiber as a new approach for regenerative medicine. Our data showed that hAMSCs aggregated in the device constitutes…
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models
2018
Colorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called consensus molecular subtypes (CMS1-4), each of which has a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed. This study was designed to determine the heterogeneity and identify the prese…
Cytotoxicity of seven naturally occurring phenolic compounds towards multi-factorial drug-resistant cancer cells
2016
Abstract Introduction In medical oncology, multi-drug resistance (MDR) of cancer cells continues to be a major impediment. We are in quest of novel anti-proliferative agents to overcome drug-resistant tumor cells. Methods In the present study, we investigated the cytotoxicity of 7 naturally occurring phenolic compounds including two isoflavonoids alpinumisoflavone ( 1 ) and laburnetin ( 2 ), one biflavonoid amentoflavone ( 3) , three lignans pycnanthulignene A ( 4 ), pycnanthulignene B ( 5 ), and syringaresinol ( 7 ) and one xanthone, euxanthone ( 6 ) against 9 drug-sensitive and MDR cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, w…
Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery
2020
Cathepsin S (CatS) is a secreted cysteine protease that cleaves certain extracellular matrix proteins, regulates antigen presentation in antigen-presenting cells (APC), and promotes M2-type macrophage and dendritic cell polarization. CatS is overexpressed in many solid cancers, and overall, it appears to promote an immune-suppressive and tumor-promoting microenvironment. While most data suggest that CatS inhibition or knockdown promotes anti-cancer immunity, cell-specific inhibition, especially in myeloid cells, appears to be important for therapeutic efficacy. This makes the design of CatS selective inhibitors and their targeting to tumor-associated M2-type macrophages (TAM) and DC an attr…
Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression.
2017
Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial muc…