Related Experiment Video
Updated: Aug 5, 2025
10:43
Preparation, Purification, and Use of Fatty Acid-containing Liposomes
Published on: February 9, 2018
54.3K
Fatty acids as molecular carriers in cleavable antifungal conjugates
Michał Nowak1, Andrzej S Skwarecki2, Joanna Pilch2
1Department of Organic Chemistry, Faculty of Chemistry, Gdańsk University of Technology, 11/12 Narutowicza St., 80-233, Gdańsk, Poland.
European Journal of Medicinal Chemistry
|March 23, 2023
Summary
New fatty acid conjugates show promise against Candida yeast infections. These compounds release 5-fluorocytosine (5-FC) inside cells, demonstrating effective in vitro antifungal activity against common pathogenic yeasts.
Area of Science:
- Medicinal Chemistry
- Antimicrobial Agents
- Mycology
Background:
- Human pathogenic yeasts, particularly Candida species, pose significant health risks.
- Development of novel antifungal agents is crucial to combat emerging resistance.
- Fatty acid conjugates offer a potential strategy for targeted drug delivery.
Purpose of the Study:
- To synthesize and evaluate the in vitro antifungal activity of fatty acid (FA) conjugates with 5-fluorocytosine (5-FC).
- To investigate the structure-activity relationship of varying fatty acid chain lengths.
- To assess the mechanism of release and cellular uptake of the active agent.
Main Methods:
- Synthesis of C2-18 fatty acid conjugates linked to 5-fluorocytosine via an intramolecular linker.
- Determination of minimal inhibitory concentrations (MIC) against various Candida species.
- Assessment of esterase hydrolysis rates and cellular uptake using fluorescent analogs.
Main Results:
- Conjugates with medium-chain fatty acids (C8-C14) exhibited potent in vitro activity against Candida spp. (MICs 2-64 μg/mL), except for Candida krusei.
- Conjugates with short (C2) or long (C16-C18) fatty acid chains showed reduced activity.
- Slower esterase hydrolysis and likely poor cellular uptake were observed for less active conjugates.
Conclusions:
- Fatty acid conjugates of 5-fluorocytosine are effective in vitro against pathogenic Candida yeasts.
- Optimal antifungal activity is associated with specific medium-chain fatty acid residues.
- Fatty acid chain length influences esterase hydrolysis and cellular uptake, impacting efficacy.
Related Concept Videos
01:32Lipids as Anchors
5.7K
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
5.7K
01:20Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Overview
18.3K
The Fischer esterification reaction was developed by the German chemist Emil Fischer in 1895. It is a condensation reaction between carboxylic acids and alcohols in an acidic medium to give esters and water.
18.3K
01:13Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism
8.1K
Carboxylic acids react with alcohols to yield esters via an acid-catalyzed condensation reaction called Fischer esterification. This is a nucleophilic acyl substitution reaction that proceeds via a tetrahedral intermediate, where a water molecule is eliminated as the leaving group.
8.1K
01:15Carboxylic Acid Derivatives: Overview
4.0K
Carboxylic acid derivatives are formed by replacing the hydroxyl group of carboxylic acids with a different functional group. The most common carboxylic acid derivatives are:
4.0K
01:23Membrane Fluidity
153.5K
Cell membranes are composed of phospholipids, proteins, and carbohydrates loosely attached to one another through chemical interactions. Molecules are generally able to move about in the plane of the membrane, giving the membrane its flexible nature called fluidity. Two other features of the membrane contribute to membrane fluidity: the chemical structure of the phospholipids and the presence of cholesterol in the membrane.
153.5K
01:28Overview of Fatty Acid Metabolism
30.9K
Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
30.9K