Synthesizing Novel Anthraquinone Natural Product-like Compounds To Investigate Protein–Ligand Interactions in Both an in Vitro and in Vivo Assay: An Integrated Research-Based Third-Year Chemical Biology Laboratory Course

2012 ◽  
Vol 89 (6) ◽  
pp. 743-749 ◽  
Author(s):  
Nancy McKenzie ◽  
James McNulty ◽  
David McLeod ◽  
Meghan McFadden ◽  
Naresh Balachandran
Keyword(s):  
Natural Product ◽  
Chemical Biology ◽  
Laboratory Course ◽  
Protein Ligand Interactions ◽  
In Vivo Assay ◽  
Integrated Research ◽  
Ligand Interactions ◽  
Biology Laboratory

scholarly journals FtsZ Interactions and Biomolecular Condensates as Potential Targets for New Antibiotics

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 254
Author(s):  
Silvia Zorrilla ◽  
Begoña Monterroso ◽  
Miguel-Ángel Robles-Ramos ◽  
William Margolin ◽  
Germán Rivas
Keyword(s):  
Cell Division ◽  
Bacterial Resistance ◽  
Protein Ligand Interactions ◽  
Protein Partners ◽  
Central Protein ◽  
Ligand Interactions ◽  
New Antibiotics ◽  
Division Process

FtsZ is an essential and central protein for cell division in most bacteria. Because of its ability to organize into dynamic polymers at the cell membrane and recruit other protein partners to form a “divisome”, FtsZ is a leading target in the quest for new antibacterial compounds. Strategies to potentially arrest the essential and tightly regulated cell division process include perturbing FtsZ’s ability to interact with itself and other divisome proteins. Here, we discuss the available methodologies to screen for and characterize those interactions. In addition to assays that measure protein-ligand interactions in solution, we also discuss the use of minimal membrane systems and cell-like compartments to better approximate the native bacterial cell environment and hence provide a more accurate assessment of a candidate compound’s potential in vivo effect. We particularly focus on ways to measure and inhibit under-explored interactions between FtsZ and partner proteins. Finally, we discuss recent evidence that FtsZ forms biomolecular condensates in vitro, and the potential implications of these assemblies in bacterial resistance to antibiotic treatment.

Evaluation of the Skin Sensitization Potential of Silica nanoparticles using in vitro and in vivo assay

2021 ◽  
Vol 350 ◽  
pp. S72
Author(s):  
D.H. Lee ◽  
S.-H. Kim ◽  
J.H. Lee ◽  
J.-Y Yang ◽  
H.-S. Shin ◽  
...  
Keyword(s):  
Silica Nanoparticles ◽  
Skin Sensitization ◽  
In Vivo Assay

Effects of a novel marine natural product: pyrano indolone alkaloid fibrinolytic compound on thrombolysis and hemorrhagic activities in vitro and in vivo

2014 ◽  
Vol 38 (8) ◽  
pp. 1530-1540 ◽  
Author(s):  
Ting Yan ◽  
Wenhui Wu ◽  
Tongwei Su ◽  
Jiajie Chen ◽  
Quangang Zhu ◽  
...  
Keyword(s):  
Natural Product ◽  
Marine Natural Product

scholarly journals Rationally designed chemokine-based toxin targeting the viral G protein-coupled receptor US28 potently inhibits cytomegalovirus infection in vivo

2015 ◽  
Vol 112 (27) ◽  
pp. 8427-8432 ◽  
Author(s):  
Katja Spiess ◽  
Mads G. Jeppesen ◽  
Mikkel Malmgaard-Clausen ◽  
Karen Krzywkowski ◽  
Kalpana Dulal ◽  
...  
Keyword(s):  
G Protein ◽  
Pseudomonas Exotoxin ◽  
Viral Pathogen ◽  
Virus Origin ◽  
Ligand Interactions ◽  
Toxin Protein ◽  
Novel Strategy ◽  
G Protein Coupled

The use of receptor–ligand interactions to direct toxins to kill diseased cells selectively has shown considerable promise for treatment of a number of cancers and, more recently, autoimmune disease. Here we move the fusion toxin protein (FTP) technology beyond cancer/autoimmune therapeutics to target the human viral pathogen, human cytomegalovirus (HCMV), on the basis of its expression of the 7TM G protein-coupled chemokine receptor US28. The virus origin of US28 provides an exceptional chemokine-binding profile with high selectivity and improved binding for the CX3C chemokine, CX3CL1. Moreover, US28 is constitutively internalizing by nature, providing highly effective FTP delivery. We designed a synthetic CX3CL1 variant engineered to have ultra-high affinity for US28 and greater specificity for US28 than the natural sole receptor for CX3CL1, CX3CR1, and we fused the synthetic variant with the cytotoxic domain of Pseudomonas Exotoxin A. This novel strategy of a rationally designed FTP provided unparalleled anti-HCMV efficacy and potency in vitro and in vivo.

Pharmacological Properties of Curcumin

2020 ◽  
pp. 235-248
Author(s):  
Anuradha Singh
Keyword(s):  
Clinical Trial ◽  
Natural Product ◽  
Mechanisms Of Action ◽  
Clinical Settings ◽  
Pharmacological Properties ◽  
Pharmacological Effects ◽  
The Poor ◽  
Cellular Factors

Curcumin, the polyphenol natural product, is a constituent of the traditional medicine known as turmeric. Extensive research over the last 50 years has indicated that this polyphenol displays potent pharmacological effects by targeting many critical cellular factors through a diverse array of mechanisms of action. However, there are some obstacles that prevent this wonder molecule to be effective in clinical settings and limit its use to topical applications only. Curcumin has recently been classified as both PAINS (panassay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. Due to likely false activity of curcumin in vitro and in vivo has resulted unsuccessful clinical trial of curcumin against several disease. The chapter will review the essential medicinal chemistry of curcumin as well as envisage a compilation and discussion on the poor bioavailability of curcumin.

scholarly journals Falcipain Inhibitors Based on the Natural Product Gallinamide A Are Potent in Vitro and in Vivo Antimalarials

2019 ◽  
Vol 62 (11) ◽  
pp. 5562-5578 ◽  
Author(s):  
Alexander Stoye ◽  
Annette Juillard ◽  
Arthur H. Tang ◽  
Jennifer Legac ◽  
Jiri Gut ◽  
...  
Keyword(s):  
Natural Product

scholarly journals In Silico Identification of Potential Natural Product Inhibitors of Human Proteases Key to SARS-CoV-2 Infection

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3822 ◽  
Author(s):  
R.P. Vivek-Ananth ◽  
Abhijit Rana ◽  
Nithin Rajan ◽  
Himansu S. Biswal ◽  
Areejit Samal
Keyword(s):  
Medicinal Plants ◽  
Natural Product ◽  
Cathepsin L ◽  
Md Simulations ◽  
Binding Energies ◽  
In Vivo Testing ◽  
Approved Drugs ◽  
Indian Medicinal Plants

Presently, there are no approved drugs or vaccines to treat COVID-19, which has spread to over 200 countries and at the time of writing was responsible for over 650,000 deaths worldwide. Recent studies have shown that two human proteases, TMPRSS2 and cathepsin L, play a key role in host cell entry of SARS-CoV-2. Importantly, inhibitors of these proteases were shown to block SARS-CoV-2 infection. Here, we perform virtual screening of 14,011 phytochemicals produced by Indian medicinal plants to identify natural product inhibitors of TMPRSS2 and cathepsin L. AutoDock Vina was used to perform molecular docking of phytochemicals against TMPRSS2 and cathepsin L. Potential phytochemical inhibitors were filtered by comparing their docked binding energies with those of known inhibitors of TMPRSS2 and cathepsin L. Further, the ligand binding site residues and non-covalent interactions between protein and ligand were used as an additional filter to identify phytochemical inhibitors that either bind to or form interactions with residues important for the specificity of the target proteases. This led to the identification of 96 inhibitors of TMPRSS2 and 9 inhibitors of cathepsin L among phytochemicals of Indian medicinal plants. Further, we have performed molecular dynamics (MD) simulations to analyze the stability of the protein-ligand complexes for the three top inhibitors of TMPRSS2 namely, qingdainone, edgeworoside C and adlumidine, and of cathepsin L namely, ararobinol, (+)-oxoturkiyenine and 3α,17α-cinchophylline. Interestingly, several herbal sources of identified phytochemical inhibitors have antiviral or anti-inflammatory use in traditional medicine. Further in vitro and in vivo testing is needed before clinical trials of the promising phytochemical inhibitors identified here.

A sensitive fluorigenic substrate for selective in vitro and in vivo assay of leukotriene A4 hydrolase activity

2013 ◽  
Vol 441 (2) ◽  
pp. 152-161 ◽  
Author(s):  
Hervé Poras ◽  
Sophie Duquesnoy ◽  
Marie-Claude Fournié-Zaluski ◽  
Céline Ratinaud-Giraud ◽  
Bernard P. Roques ◽  
...  
Keyword(s):  
Hydrolase Activity ◽  
In Vivo Assay ◽  
Leukotriene A4 Hydrolase ◽  
Leukotriene A4

scholarly journals Antiplasmodial Quinones from the Rhizomes of Kniphofia Foliosa

2013 ◽  
Vol 8 (9) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Martha Induli ◽  
Meron Gebru ◽  
Negera Abdissa ◽  
Hosea Akala ◽  
Ingrid Wekesa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Methyl Ether ◽  
Spectroscopic Data ◽  
Antimalarial Activity ◽  
In Vivo Assay

Extracts of the rhizomes of Kniphofia foliosa exhibited antiplasmodial activities against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC50 values of 3–5 μg/mL. A phenyloxanthrone, named 10-acetonylknipholone cyclooxanthrone (1) and an anthraquinone-anthrone dimer, chryslandicin 10-methyl ether (2), were isolated from the rhizomes, along with known quinones, including the rare phenylanthraquinone dimers, joziknipholones A and B. The structures of these compounds were determined based on spectroscopic data. This is the second report on the occurrence of the dimeric phenylanthraquinones in nature. In an in vitro antiplasmodial assay of the isolated compounds, activity was observed for phenylanthraquinones, anthraquinone-anthrone dimers and dimeric phenylanthraquinones, with joziknipholone A being the most active. The new compound, 10-acetonylknipholone cyclooxanthrone, also showed anti-plasmodial activity. In an in vivo assay, knipholone anthrone displayed marginal antimalarial activity.

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