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Related Concept Videos

What is Gene Expression?01:42

What is Gene Expression?

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Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
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What is Gene Expression?01:36

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A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
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Cell Specific Gene Expression01:58

Cell Specific Gene Expression

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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Cell Specific Gene Expression

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Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
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mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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Subcutaneous Infection of Methicillin Resistant Staphylococcus Aureus MRSA
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Indole-nitroimidazole conjugates as efficient manipulators to decrease the genes expression of methicillin-resistant

Zhen-Zhen Li1, Vijai Kumar Reddy Tangadanchu1, Narsaiah Battini1

  • 1Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China.

European Journal of Medicinal Chemistry
|July 9, 2019
PubMed
Summary
This summary is machine-generated.

Novel enone-bridged indole nitroimidazole compounds show potent activity against methicillin-resistant Staphylococcus aureus (MRSA). Compound 4b inhibits MRSA growth, prevents resistance, and demonstrates low cytotoxicity, offering a promising new therapeutic strategy.

Keywords:
GeneIndoleMRSAMechanismNitroimidazole

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Area of Science:

  • Medicinal Chemistry
  • Antimicrobial Resistance
  • Drug Discovery

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant global health threat due to widespread antibiotic resistance.
  • Development of novel synthetic antibiotics is crucial to overcome existing resistance mechanisms.

Purpose of the Study:

  • To design and synthesize novel enone-bridged indole nitroimidazole scaffolds as potential anti-MRSA agents.
  • To investigate the biological activities and resistance-preventing capabilities of these new compounds.

Main Methods:

  • Synthesis of novel enone-bridged indole nitroimidazole derivatives.
  • Bioassay to determine Minimum Inhibitory Concentration (MIC) against MRSA.
  • Mechanism of action studies including DNA intercalation, membrane permeation, PBP2a binding, and gene expression analysis.
  • Human serum albumin (HSA) binding and transport studies.
  • Cytotoxicity assays using the BEAS-2B cell line.

Main Results:

  • Compound 4b demonstrated significant inhibition of MRSA with an MIC of 1 μg/mL.
  • Compound 4b effectively prevented the development of bacterial resistance.
  • Mechanism studies revealed DNA intercalation, membrane permeation, PBP2a binding, and reduced expression of key MRSA genes.
  • The 4b-HSA system, enhanced by metal ions, showed improved supramolecular transport.
  • Compound 4b exhibited low cytotoxicity against normal lung epithelial cells.

Conclusions:

  • Novel enone-bridged indole nitroimidazole scaffolds are effective against MRSA.
  • Compound 4b possesses multiple mechanisms of action, including PBP2a binding and DNA intercalation, contributing to its efficacy and resistance-prevention.
  • The compound's interaction with HSA suggests potential for improved drug delivery and therapeutic applications.