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A Time-Efficient Fluorescence Spectroscopy-Based Assay for Evaluating Actin Polymerization Status in Rodent and Human Brain Tissues
Published on: June 3, 2021
Bioactive natural and semisynthetic latrunculins
Khalid A El Sayed1, Diaa T A Youssef, Dario Marchetti
1Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Louisiana 71209, USA. elsayed@ulm.edu
Journal of Natural Products
|February 28, 2006
Summary
Marine natural products called latrunculins, isolated from the Red Sea sponge Negombata magnifica, disrupt actin organization. These compounds show significant antimicrobial and antiangiogenic potential for drug development.
Area of Science:
- Marine Natural Products Chemistry
- Biochemistry
- Pharmacology
Background:
- Marine-derived macrolides, specifically latrunculins from the Red Sea sponge Negombata magnifica, are unique for their reversible binding to actin monomers.
- Latrunculins share structural similarities with known antimicrobial and antiangiogenic compounds, suggesting broad therapeutic potential.
Purpose of the Study:
- To isolate and characterize new latrunculins from N. magnifica.
- To synthesize novel latrunculin analogues through semisynthetic modifications.
- To evaluate the biological activities of natural and semisynthetic latrunculins, including antiangiogenic, antimigratory, and antimicrobial effects.
Main Methods:
- Isolation and purification of latrunculins A, B, and T from N. magnifica.
- Semisynthetic modifications of latrunculin B, including acetylation, acetalization, and N-hydroxymethylation.
- In vitro assays to assess antiangiogenic (chick chorioallantoic membrane assay), antimigratory (Boyden's chamber assay, wound-healing assay), and antimicrobial (against Candida albicans, Saccharomyces cerevisiae, Staphylococcus aureus, Bacillus cereus) activities.
Main Results:
- Isolation of several grams of latrunculin B and a new analogue, latrunculin T.
- Synthesis of four new and two known semisynthetic latrunculin analogues.
- 15-O-methyllatrunculin B demonstrated promising antiangiogenic and antimigratory activities.
- Latrunculin B and N-acetyllatrunculin B exhibited potent antimigratory effects in a wound-healing assay.
- Both natural and semisynthetic latrunculins displayed significant antimicrobial activity against tested pathogens.
Conclusions:
- Latrunculins represent a novel class of marine natural products with significant biological activities.
- Semisynthetic modifications can yield analogues with enhanced therapeutic properties.
- Latrunculins are promising lead compounds for the development of new anticancer and antimicrobial agents.
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