title: Latrunculin with a highly oxidized thiazolidinone ring: structure assignment and actin docking.
abstract: 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.
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
authors.forename: Safwat A
authors.initials: SA
authors.lastname: Ahmed
authors.forename: Srinivas
authors.initials: S
authors.lastname: Odde
authors.forename: Pankaj R
authors.initials: PR
authors.lastname: Daga
authors.forename: John J
authors.initials: JJ
authors.lastname: Bowling
authors.forename: Mostafa K
authors.initials: MK
authors.lastname: Mesbah
authors.forename: Diaa T
authors.initials: DT
authors.lastname: Youssef
authors.forename: Sherief I
authors.initials: SI
authors.lastname: Khalifa
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Doerksen
authors.forename: Mark T
authors.initials: MT
authors.lastname: Hamann
mesh_terms: 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
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D053778:Thiazolidines; C037068:latrunculin B; D010100:Oxygen; C037067:latrunculin A