Polyamine-based analogs and conjugates as antikinetoplastid agents.
Elodie Jagu1, Sébastien Pomel2, Stéphanie Pethe1
1Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), CNRS, Univ Paris Sud, Université Paris-Saclay, 15 rue Georges Clemenceau, 91405 Orsay Cedex, France.
European Journal of Medicinal Chemistry
|September 9, 2017
Summary
Polyamines are essential for Kinetoplastid survival. This review highlights polyamine derivatives as promising candidates for developing new antikinetoplastid chemotherapy drugs.
Area of Science:
- Biochemistry
- Parasitology
- Medicinal Chemistry
Background:
- Naturally occurring polyamines (putrescine, spermidine, spermine) are vital for Kinetoplastid growth and survival.
- Kinetoplastids regulate polyamine levels through biosynthesis and active transport.
- Targeting polyamine metabolism presents a viable strategy for antikinetoplastid drug development.
Purpose of the Study:
- To comprehensively review polyamine derivatives with demonstrated antikinetoplastid activity.
- To analyze structure-activity relationships of these compounds.
- To identify promising candidates for future antikinetoplastid drug discovery.
Main Methods:
- Literature review of polyamine derivatives with antikinetoplastid activity.
- Categorization of derivatives into diamine, triamine, and tetramine classes.
- Analysis of in vitro and in vivo activity data and structure-activity relationships.
Main Results:
- Numerous polyamine derivatives exhibiting antikinetoplastid activity have been identified.
- Structure-activity relationship analysis reveals key molecular features for efficacy.
- Specific diamine, triamine, and tetramine derivatives show significant potential.
Conclusions:
- Polyamine derivatives represent a promising therapeutic avenue for Kinetoplastid infections.
- Further investigation into the most promising structures could lead to novel antikinetoplastid drugs.
- Targeting polyamine metabolism remains a key strategy in combating Kinetoplastid diseases.
More Related Videos
08:55Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles PPAs and Related Biomaterials
Published on: June 25, 2018
8.6K
08:48Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation
Published on: January 26, 2016
12.5K
Related Concept Videos
01:11Aryldiazonium Salts to Azo Dyes: Diazo Coupling
3.7K
The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the para...
3.7K
01:29Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
1.1K
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
1.1K
01:10Drugs that Destabilize Microtubules
4.1K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
4.1K
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
2.8K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
2.8K
01:29Cholinergic Antagonists: Chemistry and Structure-Activity Relationship
2.9K
Cholinergic antagonists bind to cholinergic receptors and limit the effects of acetylcholine and other cholinergic agonists. Based on the specific cholinergic receptor affinity, these antagonists are classified as muscarinic or nicotinic. Anticholinergics interrupt parasympathetic innervations while sympathetic innervations remain uninterrupted. Muscarinic antagonists are also called 'muscarinic antagonists', 'antimuscarinics', or 'parasympatholytics'. Nicotinic...
2.9K
01:26Anticholinesterase Agents: Poisoning and Treatment
1.8K
Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
1.8K