Broad Assessment of Bioactivity of a Collection of Spiroindane Pyrrolidines Through “Cell Painting”

2020 ◽  
Author(s):  
Zarko Boskovic ◽  
Manvendra Singh ◽  
Zachary Pearson ◽  
Nathan Garza
Keyword(s):  
Biological Activity ◽  
Small Molecules ◽  
Functional Groups ◽  
Organelle Morphology

A collection of small molecules has been synthesized by composing photo-cycloaddition, C-H functionalization, and N-capping strategies. Multidimensional biological fingerprints of molecules comprising this collection have been recorded as changes in cell and organelle morphology. This untargeted, phenotypic approach allowed for a broad assessment of biological activity to be determined. Reproducibility and the magnitude of measured fingerprints revealed activity of several treatments. Reactive functional groups, such as imines, dominated the observed activity. Two non-reactive candidate compounds with distinct bioactivity fingerprints were identified, as well.

Broad Assessment of Bioactivity of a Collection of Spiroindane Pyrrolidines Through “Cell Painting”

2020 ◽  
Author(s):  
Zarko Boskovic ◽  
Manvendra Singh ◽  
Zachary Pearson ◽  
Nathan Garza
Keyword(s):  
Biological Activity ◽  
Small Molecules ◽  
Functional Groups ◽  
Organelle Morphology

A collection of small molecules has been synthesized by composing photo-cycloaddition, C-H functionalization, and N-capping strategies. Multidimensional biological fingerprints of molecules comprising this collection have been recorded as changes in cell and organelle morphology. This untargeted, phenotypic approach allowed for a broad assessment of biological activity to be determined. Reproducibility and the magnitude of measured fingerprints revealed activity of several treatments. Reactive functional groups, such as imines, dominated the observed activity. Two non-reactive candidate compounds with distinct bioactivity fingerprints were identified, as well.

Naphthoquinone Derivatives Isolated from Plants: Recent Advances in Biological Activity

2020 ◽  
Vol 20 (19) ◽  
pp. 2019-2035
Author(s):  
Esmaeil Sheikh Ahmadi ◽  
Amir Tajbakhsh ◽  
Milad Iranshahy ◽  
Javad Asili ◽  
Nadine Kretschmer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Biological Activity ◽  
Small Molecules ◽  
Anticancer Activity ◽  
Clinical Significance ◽  
Phase Ii ◽  
Biological Activities ◽  
Phase Ii Clinical Trials ◽  
Naturally Occurring ◽  
The Subject

Naturally occurring naphthoquinones (NQs) comprising highly reactive small molecules are the subject of increasing attention due to their promising biological activities such as antioxidant, antimicrobial, apoptosis-inducing activities, and especially anticancer activity. Lapachol, lapachone, and napabucasin belong to the NQs and are in phase II clinical trials for the treatment of many cancers. This review aims to provide a comprehensive and updated overview on the biological activities of several new NQs isolated from different species of plants reported from January 2013 to January 2020, their potential therapeutic applications and their clinical significance.

scholarly journals Synthesis and Biological Activity of Brassinosteroid Analogues with a Nitrogen-Containing Side Chain

2020 ◽  
Vol 22 (1) ◽  
pp. 155
Author(s):  
Mikhail V. Diachkov ◽  
Karoll Ferrer ◽  
Jana Oklestkova ◽  
Lucie Rarova ◽  
Vaclav Bazgier ◽  
...  
Keyword(s):  
Biological Activity ◽  
Functional Groups ◽  
Side Chain ◽  
Biotic And Abiotic Stresses ◽  
Short Side ◽  
Arabidopsis Root ◽  
Physiological Processes ◽  
Growth Promoting ◽  
The Impact ◽  
Brassinosteroid Analogues

Brassinosteroids are a class of plant hormones that regulate a broad range of physiological processes such as plant growth, development and immunity, including the suppression of biotic and abiotic stresses. In this paper, we report the synthesis of new brassinosteroid analogues with a nitrogen-containing side chain and their biological activity on Arabidopis thaliana. Based on molecular docking experiments, two groups of brassinosteroid analogues were prepared with short and long side chains in order to study the impact of side chain length on plants. The derivatives with a short side chain were prepared with amide, amine and ammonium functional groups. The derivatives with a long side chain were synthesized using amide and ammonium functional groups. A total of 25 new brassinosteroid analogues were prepared. All 25 compounds were tested in an Arabidopsis root sensitivity bioassay and cytotoxicity screening. The synthesized substances showed no significant inhibitory activity compared to natural 24-epibrassinolide. In contrast, in low concentration, several compounds (8a, 8b, 8e, 16e, 22a and 22e) showed interesting growth-promoting activity. The cytotoxicity assay showed no toxicity of the prepared compounds on cancer and normal cell lines.

The Geometry Structure and Molecular Vibrational Property of the Zeatin

2013 ◽  
Vol 634-638 ◽  
pp. 33-36
Author(s):  
Kun Yuan ◽  
Yuan Cheng Zhu ◽  
Ling Juan Yang ◽  
Zhi Bo Wang
Keyword(s):  
Biological Activity ◽  
Density Function ◽  
Functional Groups ◽  
Plant Tissue ◽  
Biological Activities ◽  
Vibrational Property ◽  
Geometry Structure ◽  
Research Fields ◽  
Ft Ir

Zeatin belongs to the derivation of purine, and the C=C is one of the functional groups in the zeatin structure. So, there are trans- and cis- structures for the zeatin molecule. Interestingly, the trans-zeatin has biological activities, but the cis-zeatin has no obvious biological activity. The trans-zeatin is the first separated cell cytokinins from the plant tissue. And the zeatin, especially trans-zeatin has important and extensive applications in many research fields. In this study, the Geometries of the trans-zeatin and cis-zeatin were optimized by using the density function Becke, three-parameter, Lee-Yang-Parr, DFT/B3LYP/6-31G method. Additionally, FT-IR experiments were conducted for the trans-zeatin. The geometry structures and molecular vibrational property of the zeatin were simply discussed.

scholarly journals Reactivity of Copper Electrodes towards Functional Groups and Small Molecules in the Context of CO2 Electro-Reductions

Catalysts ◽  
2017 ◽  
Vol 7 (5) ◽  
pp. 161 ◽  
Author(s):  
Bernhard Schmid ◽  
Christian Reller ◽  
Sebastian Neubauer ◽  
Maximilian Fleischer ◽  
Romano Dorta ◽  
...  
Keyword(s):  
Small Molecules ◽  
Functional Groups ◽  
Copper Electrodes

scholarly journals Repression of Salmonella Host Cell Invasion by Aromatic Small Molecules from the Human Fecal Metabolome

2017 ◽  
Vol 83 (19) ◽  
Author(s):  
Rafael J. M. Peixoto ◽  
Eduardo S. Alves ◽  
Melody Wang ◽  
Rosana B. R. Ferreira ◽  
Alessandra Granato ◽  
...  
Keyword(s):  
Biological Activity ◽  
Small Molecules ◽  
Host Cell ◽  
Small Molecule ◽  
Cell Invasion ◽  
Salmonella Enterica ◽  
Chemical Diversity ◽  
Host Cell Invasion ◽  
Human Gut ◽  
Content Type

ABSTRACT The human microbiome is a collection of microorganisms that inhabit every surface of the body that is exposed to the environment, generally coexisting peacefully with their host. These microbes have important functions, such as producing vitamins, aiding in maturation of the immune system, and protecting against pathogens. We have previously shown that a small-molecule extract from the human fecal microbiome has a strong repressive effect on Salmonella enterica serovar Typhimurium host cell invasion by modulating the expression of genes involved in this process. Here, we describe the characterization of this biological activity. Using a series of purification methods, we obtained fractions with biological activity and characterized them by mass spectrometry. These experiments revealed an abundance of aromatic compounds in the bioactive fraction. Selected compounds were obtained from commercial sources and tested with respect to their ability to repress the expression of hilA, the gene encoding the master regulator of invasion genes in Salmonella. We found that the aromatic compound 3,4-dimethylbenzoic acid acts as a strong inhibitor of hilA expression and of invasion of cultured host cells by Salmonella. Future studies should reveal the molecular details of this phenomenon, such as the signaling cascades involved in sensing this bioactive molecule. IMPORTANCE Microbes constantly sense and adapt to their environment. Often, this is achieved through the production and sensing of small extracellular molecules. The human body is colonized by complex communities of microbes, and, given their biological and chemical diversity, these ecosystems represent a platform where the production and sensing of molecules occur. In previous work, we showed that small molecules produced by microbes from the human gut can significantly impair the virulence of the enteric pathogen Salmonella enterica. Here, we describe a specific compound from the human gut that produces this same effect. The results from this work not only shed light on an important biological phenomenon occurring in our bodies but also may represent an opportunity to develop drugs that can target these small-molecule interactions to protect us from enteric infections and other diseases.

scholarly journals Harnessing the Intrinsic Photochemistry of Isoxazoles for the Development of Chemoproteomic Crosslinking Methods

2021 ◽  
Author(s):  
Marshall G. Lougee ◽  
Vinayak Vishnu Pagar ◽  
Hee Jong Kim ◽  
Samantha X. Pancoe ◽  
Robert H. Mach ◽  
...  
Keyword(s):  
Protein Binding ◽  
Small Molecules ◽  
Functional Groups ◽  
Ex Vivo ◽  
Initial Report ◽  
Biologically Relevant ◽  
Fine Grained ◽  
Wide Range ◽  
Unique Method

Photo-crosslinking is a powerful technique for identifying both coarse- and fine-grained information on protein binding by small molecules. However, the scope of useful functional groups remains limited, with most studies focusing on diazirine, aryl azide, or benzophenone-containing molecules. Here, we report a unique method for photo-crosslinking, employing the intrinsic photochemistry of the isoxazole, a common heterocycle in medicinal chemistry, to offer an alternative to existing strategies using more perturbing, extrinsic crosslinkers. In this initial report, this technique is applied both in vitro and ex vivo, used in a variety of common chemoproteomic workflows, and validated across multiple proteins, demonstrating the utility of isoxazole photo-crosslinking in a wide range of biologically relevant experiments.

Chemotherapeutic Applications of Folate Prodrugs: A Review

2021 ◽  
Vol 19 (8) ◽  
pp. 99-112
Author(s):  
Yasser Fakri Mustafa
Keyword(s):  
Biological Activity ◽  
Drug Design ◽  
Small Molecules ◽  
Significant Interaction ◽  
Active Drug ◽  
Folate Receptor ◽  
The Other ◽  
Technological Innovations ◽  
Drug Molecule ◽  
Drug Conjugates

Several techniques to assisting in the drug design and discovery stages have been developed during the last several decades. The bulk of these techniques aimed to find novel chemical entities that had the greatest significant interaction with the targeted receptors or enzymes while providing the least degree of risk of unwanted interactions. This approach, on the other hand, is time-consuming and expensive, as it requires the screening of thousands of molecules for biological activity, with only one making it to market. The prodrug strategy, in which the active drug molecule is disguised by a promoiety to change its undesirable characteristics, is one of the most appealing and promising methods. The folate receptor (FR)-targeted systems may also open the path for more advanced drug conjugates, especially because this receptor is now being targeted by a variety of technological innovations, including nanoparticles, small molecules, and protein-based technologies, resulting in a wealth of experience in the discipline.

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