Diamond Publications - Search Results

Search Again...

These results include publications that have not yet been reviewed and processed by Diamond Light Source. To view only processed publications click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

One item found (0 items not approved).

Instruments / Technical Area	Publication Details	Published	Actions
I04-Macromolecular Crystallography	Chroman-4-one derivatives targeting pteridine reductase 1 and showing anti-parasitic activity Flavio Di Pisa , Giacomo Landi , Lucia Dello Iacono , Cecilia Pozzi , Chiara Borsari , Stefania Ferrari , Matteo Santucci , Nuno Santarem , Anabela Cordeiro-Da-Silva , Carolina Moraes , Laura Alcantara , Vanessa Fontana , Lucio Freitas-Junior , Sheraz Gul , Maria Kuzikov , Birte Behrens , Ina Pöhner , Rebecca Wade , Maria Costi , Stefano Mangani Molecules 22 DOI: 10.3390/molecules22030426 Diamond Proposal Number(s): [8574] Open Access Show Abstract ▼ Abstract: Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues (1–3) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes (Trypanosoma brucei PTR1–TbPTR1 and Leishmania major–LmPTR1) and parasites (Trypanosoma brucei and Leishmania infantum). A crystal structure of TbPTR1 in complex with compound 1 and the first crystal structures of LmPTR1-flavanone complexes (compounds 1 and 3) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants.	Mar 2017

Instruments / Technical Area

Publication Details

Published

Actions

I04-Macromolecular Crystallography

Chroman-4-one derivatives targeting pteridine reductase 1 and showing anti-parasitic activity