152213-66-6Relevant articles and documents
Formal synthesis of (-)-flustramine B and its absolute configuration assignment by vibrational circular dichroism exciton chirality
Cordero-Rivera, Reyna E.,Meléndez-Rodríguez, Myriam,Suárez-Castillo, Oscar R.,Bautista-Hernández, Claudia I.,Trejo-Carbajal, Nayely,Cruz-Borbolla, Julián,Castelán-Duarte, Luis E.,Morales-Ríos, Martha S.,Joseph-Nathan, Pedro
, p. 710 - 720 (2015)
Abstract A formal synthesis of the natural product (-)-flustramine B (3) is described, together with an easy and reliable approach for the absolute configuration assignment of a series of (3R,14S)- and (3S,14S)-oxindolylacetylphenyloxazolidinones 4, 6, 13
Phidianidine A and Synthetic Analogues as Naturally Inspired Marine Antifoulants
Labriere, Christophe,Elumalai, Vijayaragavan,Staffansson, Jannie,Cervin, Gunnar,Le Norcy, Tiffany,Denardou, Hugo,Réhel, Karine,Moodie, Lindon W. K.,Hellio, Claire,Pavia, Henrik,Hansen, J?rn H.,Svenson, Johan
, p. 3413 - 3423 (2020/11/23)
Stationary and slow-moving marine organisms regularly employ a natural product chemical defense to prevent being colonized by marine micro- and macroorganisms. While these natural antifoulants can be structurally diverse, they often display highly conserved chemistries and physicochemical properties, suggesting a natural marine antifouling pharmacophore. In our current report, we investigate the marine natural product phidianidine A, which displays several chemical properties found in highly potent marine antifoulants. Phidianidine A and synthetic analogues were screened against the settlement and metamorphosis of Amphibalanus improvisus cyprids, and several of the compounds displayed inhibitory activities at low micromolar concentrations with IC50 values down to 0.7 μg/mL observed. The settlement study highlights that phidianidine A is a potent natural antifoulant and that the scaffold can be tuned to generate simpler and improved synthetic analogues. The bioactivity is closely linked to the size of the compound and to its basicity. The study also illustrates that active analogues can be prepared in the absence of the natural constrained 1,2,4-oxadiazole ring. A synthetic lead analogue of phidianidine A was incorporated in a coating and included in antifouling field trials, where it was shown that the coating induced potent inhibition of marine bacteria and microalgae settlement.
The Fragment-Based Development of a Benzofuran Hit as a New Class of Escherichia coli DsbA Inhibitors
Duncan, Luke F.,Wang, Geqing,Ilyichova, Olga V.,Scanlon, Martin J.,Heras, Bego?a,Abbott, Belinda M.
, (2019/10/28)
A fragment-based drug discovery approach was taken to target the thiol-disulfide oxidoreductase enzyme DsbA from Escherichia coli (EcDsbA). This enzyme is critical for the correct folding of virulence factors in many pathogenic Gram-negative bacteria, and small molecule inhibitors can potentially be developed as anti-virulence compounds. Biophysical screening of a library of fragments identified several classes of fragments with affinity to EcDsbA. One hit with high mM affinity, 2-(6-bromobenzofuran-3-yl)acetic acid (6), was chemically elaborated at several positions around the scaffold. X-ray crystal structures of the elaborated analogues showed binding in the hydrophobic binding groove adjacent to the catalytic disulfide bond of EcDsbA. Binding affinity was calculated based on NMR studies and compounds 25 and 28 were identified as the highest affinity binders with dissociation constants (KD) of 326 ± 25 and 341 ± 57 μM respectively. This work suggests the potential to develop benzofuran fragments into a novel class of EcDsbA inhibitors.
