Latrunculin with a highly oxidized thiazolidinone ring: structure assignment and actin docking.
A new latrunculin, oxalatrunculin B (3), was isolated from Red Sea sponge Negombata corticata. Extensive spectroscopic analysis revealed an unprecedented heterocycle in which the rare thiazolidinone ring found in latrunculins was oxidized with three additional oxygens. An actin polymerization inhibition assay agreed with MM-PBSA free energy calculations that 3 binds more weakly than latrunculin B to actin. Significant antifungal and anticancer activity of 3 was found, suggesting an alternate target in addition to actin for latrunculin bioactivity.
Ahmed
Safwat A
SA
Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
Odde
Srinivas
S
Daga
Pankaj R
PR
Bowling
John J
JJ
Mesbah
Mostafa K
MK
Youssef
Diaa T
DT
Khalifa
Sherief I
SI
Doerksen
Robert J
RJ
Hamann
Mark T
MT
D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D053778:Thiazolidines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D053778:Thiazolidines; C037068:latrunculin B; D010100:Oxygen; C037067:latrunculin A