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

Safwat A Ahmed; Srinivas Odde; Pankaj R Daga; John J Bowling; Mostafa K Mesbah; Diaa T Youssef; Sherief I Khalifa; Robert J Doerksen; Mark T Hamann

doi:10.1021/ol7020675

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

Journal article

Peer reviewed

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

Safwat A Ahmed, Srinivas Odde, Pankaj R Daga, John J Bowling, Mostafa K Mesbah, Diaa T Youssef, Sherief I Khalifa, Robert J Doerksen and Mark T Hamann

Organic letters, Vol.9(23), pp.4773-4776

08/11/2007

DOI: https://doi.org/10.1021/ol7020675

PMCID: PMC2529398

PMID: 17929935

Abstract

Actins - chemistry

Actins - metabolism

Binding Sites

Bridged Bicyclo Compounds, Heterocyclic - chemistry

Bridged Bicyclo Compounds, Heterocyclic - metabolism

Bridged Bicyclo Compounds, Heterocyclic - pharmacology

Cell Line, Tumor

Cell Survival - drug effects

Computer Simulation

Humans

Magnetic Resonance Spectroscopy

Models, Molecular

Oxygen - chemistry

Protein Structure, Tertiary

Thiazolidines - chemistry

Thiazolidines - metabolism

Thiazolidines - pharmacology

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.

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Title: Latrunculin with a highly oxidized thiazolidinone ring: structure assignment and actin docking
Creators - without role: Safwat A Ahmed - Suez Canal University
Srinivas Odde - University of Mississippi
Pankaj R Daga - University of Mississippi
John J Bowling - University of Mississippi
Mostafa K Mesbah - University of Mississippi
Diaa T Youssef - University of Mississippi
Sherief I Khalifa - University of Mississippi
Robert J Doerksen - University of Mississippi
Mark T Hamann - University of Mississippi
Publication Details: Organic letters, Vol.9(23), pp.4773-4776
Grant note: C06 RR 14503-01 / NCRR NIH HHS R01 AI036596 / NIAID NIH HHS 1R01 AI 36596 / NIAID NIH HHS C06 RR014503 / NCRR NIH HHS R01 AI036596-08 / NIAID NIH HHS
Identifiers: 9937609908331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article