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Related Concept Videos

Prodrugs01:30

Prodrugs

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Prodrugs are a class of pharmaceutical compounds that undergo a biotransformation process within the body to be converted into a pharmacologically active drug. Prodrugs are designed to improve the therapeutic properties of the parent drug, such as enhancing bioavailability, increasing stability, or reducing toxicity. The concept of prodrugs revolves around modifying the chemical structure of the original drug to make it more effective or convenient for administration.
Prodrugs help overcome...
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Drug Biotransformation: Overview01:16

Drug Biotransformation: Overview

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Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
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Cycloaddition Reactions: MO Requirements for Photochemical Activation01:12

Cycloaddition Reactions: MO Requirements for Photochemical Activation

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Some cycloaddition reactions are activated by heat, while others are initiated by light. For example, a [2 + 2] cycloaddition between two ethylene molecules occurs only in the presence of light. It is photochemically allowed but thermally forbidden.
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Drug Metabolism: Phase I Reactions01:17

Drug Metabolism: Phase I Reactions

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A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
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Drug Metabolism: Phase II Reactions01:14

Drug Metabolism: Phase II Reactions

3.9K
Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
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Reduction of Alkenes: Asymmetric Catalytic Hydrogenation02:17

Reduction of Alkenes: Asymmetric Catalytic Hydrogenation

3.3K
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
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Chemoselective Modification of Viral Surfaces via Bioorthogonal Click Chemistry
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Progress in controllable bioorthogonal catalysis for prodrug activation.

Xia Liu1, Tingjing Huang1, Zhaowei Chen1,2

  • 1MOE Key Laboratory for Analytical Science of Food Safety and Biology, and Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry, Fuzhou University, Fuzhou 350108, P. R. China. chenzw@fzu.edu.cn.

Chemical Communications (Cambridge, England)
|October 4, 2023
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Bioorthogonal catalysis uses metal catalysts for prodrug activation in the body. Engineered catalysts offer precise, on-demand drug release, minimizing side effects for better disease therapy.

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Area of Science:

  • Catalysis
  • Bioorganic Chemistry
  • Medicinal Chemistry

Background:

  • Bioorthogonal catalysis, mediated by abiotic metals, operates within biological systems without disrupting native biochemical processes.
  • This field has seen significant growth in prodrug delivery applications over recent decades.
  • Despite advancements in bioorthogonal reactions and transition metal catalysts (TMCs), *in vivo* prodrug activation remains challenging.

Purpose of the Study:

  • To review recent progress in controllable bioorthogonal catalysis systems for prodrug activation.
  • To emphasize strategies for engineering TMCs for precise control over drug release.
  • To discuss challenges and future directions in applying controllable bioorthogonal catalysis for disease therapy.

Main Methods:

  • Review of literature on bioorthogonal catalysis and prodrug delivery.
  • Analysis of strategies for designing targeted and stimulus-responsive TMCs.
  • Discussion of engineering approaches for controlled chemical transformations in complex biological systems.

Main Results:

  • Engineered TMCs with targeting and stimulus-responsive properties enable controlled *in vivo* prodrug activation.
  • On-demand drug activation strategies mitigate off-target toxicity.
  • Significant progress has been made in developing new bioorthogonal reactions and optimizing TMC performance.

Conclusions:

  • Controllable bioorthogonal catalysis holds great promise for targeted drug delivery and reduced toxicity.
  • Further engineering of TMCs is crucial for translating these systems into clinical applications.
  • Future research should focus on overcoming challenges for effective disease therapy.