Latrunculin with a highly oxidized thiazolidinone ring: structure assignment and actin docking

Area of Science:

• Marine natural products chemistry
• Chemical biology
• Drug discovery

Background:

• Latrunculins are marine natural products known for their ability to inhibit actin polymerization.
• The sponge Negombata corticata is a source of bioactive compounds.
• Understanding the structure-activity relationships of latrunculins is crucial for developing new therapeutic agents.

Purpose of the Study:

• To isolate and characterize a new latrunculin derivative from the Red Sea sponge Negombata corticata.
• To investigate the binding affinity of the new compound to actin.
• To evaluate the biological activities, including antifungal and anticancer properties, of the novel compound.

Main Methods:

• Isolation and purification of oxalatrunculin B from sponge extracts.
• Extensive spectroscopic analysis (NMR, MS) for structural elucidation.
• Actin polymerization inhibition assays.
• Molecular modeling (MM-PBSA) for binding energy calculations.
• Antifungal and anticancer activity screening.

Main Results:

• A new latrunculin, oxalatrunculin B (3), was isolated and its structure determined.
• Oxalatrunculin B features an unprecedented heterocycle with an oxidized thiazolidinone ring.
• MM-PBSA calculations and experimental assays showed weaker binding of oxalatrunculin B to actin compared to latrunculin B.
• Oxalatrunculin B demonstrated significant antifungal and anticancer activities.

Conclusions:

• Oxalatrunculin B represents a novel structural class of latrunculins.
• The compound's bioactivity may involve targets beyond actin polymerization.
• Oxalatrunculin B shows promise as a lead compound for developing new antifungal and anticancer drugs.