Related Experiment Video
Updated: Jul 17, 2026
09:26
Cellular Lipid Extraction for Targeted Stable Isotope Dilution Liquid Chromatography-Mass Spectrometry Analysis
Published on: November 17, 2011
Novel side chain modified Delta8(14)-15-ketosterols.
Alexander Yu Misharin1, Vitali S Ivanov, Arif R Mehtiev
1V.N. Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, Russia.
Steroids
|February 9, 2007
Summary
Researchers synthesized novel Delta8(14)-15-ketosterols from ergosterol. One derivative, (22R,23R)-3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one, potently inhibited sterol biosynthesis in Hep G2 cells.
Area of Science:
- Steroid chemistry
- Biochemistry
- Cell biology
Background:
- Ergosterol is a key sterol in fungal cell membranes.
- Sterol biosynthesis pathways are crucial for cell function and are targets for drug development.
- Delta8(14)-15-ketosterols represent a class of compounds with potential biological activity.
Purpose of the Study:
- To synthesize novel Delta8(14)-15-ketosterols with modified side chains starting from ergosterol.
- To evaluate the cytotoxicity of these novel compounds in human hepatoma Hep G2 cells.
- To assess their effects on sterol biosynthesis in Hep G2 cells.
Main Methods:
- Multi-step chemical synthesis starting from ergosteryl acetate.
- Characterization of synthesized ketosterols.
- Cytotoxicity assays on Hep G2 cells.
- Sterol biosynthesis inhibition assays using Hep G2 cells.
Main Results:
- Five novel Delta8(14)-15-ketosterols were successfully synthesized.
- (22R,23R)-3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one demonstrated potent inhibition of sterol biosynthesis (IC(50)=0.6+/-0.2 microM).
- (22R,23R)-5alpha-ergost-8(14)-en-15-on-3beta,22,23-triol showed the highest cytotoxicity (TC(50)=12+/-3 microM).
Conclusions:
- Novel Delta8(14)-15-ketosterols can be synthesized from ergosterol.
- Specific structural modifications lead to potent inhibition of sterol biosynthesis.
- The synthesized compounds exhibit varying degrees of cytotoxicity, with potential therapeutic applications.
Related Concept Videos
02:33Stereoisomerism of Cyclic Compounds
In this lesson, we delve into the role of ring conformation and its stability, which determines the spatial arrangement and, consequently, the molecular symmetry and stereoisomerism of cyclic compounds. 1,2-Dimethylcyclohexane is used as a case study to evaluate the possible number of stereoisomers. Here, given the multiple (n = 2) chiral centers, there are 2n = 4 possible configurations that lack a plane of symmetry, as the ring skeleton exists in a non-planar chair conformation. In addition,...
01:18Directing and Steric Effects in Disubstituted Benzene Derivatives
When disubstituted benzenes undergo electrophilic substitution, the product distribution depends on the directing effect of both substituents. When the directing effects of both substituents reinforce each other, a single product is obtained. For example, bromination of p-nitrotoluene occurs ortho to the methyl group and meta to the nitro group, which is the same position, resulting in a single product. However, if the directing effects of the two groups oppose each other, the more strongly...
01:10Radical Reactivity: Steric Effects
The presence of electron-donating, electron-withdrawing, or conjugating groups adjacent to a radical center, imparts electronic stabilization to the radicals. Examples of such electronically-stabilized radicals are triphenylmethyl, tetramethylpiperidine‐N‐oxide, and 2,2‐diphenyl‐1‐picrylhydrazyl. These radicals are remarkably stable and are known as persistent radicals. Some of the persistent radicals can even be isolated and purified.
Along with electronic factors, steric factors also account...
Along with electronic factors, steric factors also account...
02:32Stereoisomers
On the basis of mirror symmetry, stereoisomers of an organic molecule can be further classified into diastereomers and enantiomers. Diastereomers are stereoisomers that are not mirror images of each other. Substituted alkenes, such as the cis and trans isomers of 2-butene, are diastereomers, as these molecules exhibit different spatial orientations of their constituent atoms, are not mirror images of each other, and do not interconvert. Here, the interconversion is suppressed due to restricted...
02:52Stereoisomerism
Isomerism in Complexes
Isomers are different chemical species that have the same chemical formula.
Transition metal complexes often exist as geometric isomers, in which the same atoms are connected through the same types of bonds but with differences in their orientation in space. Coordination complexes with two different ligands in the cis and trans positions from a ligand of interest form isomers. For example, the octahedral [Co(NH3)4Cl2]+ ion has two isomers (Figure 1) In the cis...
Isomers are different chemical species that have the same chemical formula.
Transition metal complexes often exist as geometric isomers, in which the same atoms are connected through the same types of bonds but with differences in their orientation in space. Coordination complexes with two different ligands in the cis and trans positions from a ligand of interest form isomers. For example, the octahedral [Co(NH3)4Cl2]+ ion has two isomers (Figure 1) In the cis...
01:28Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
The Diels–Alder reaction is one of the robust methods for synthesizing unsaturated six-membered rings. The reaction involves a concerted cyclic movement of six π electrons: four π electrons from the diene and two π electrons from the dienophile.