<i>N</i>¹‑Fluoroalkyltryptophan Analogues: Synthesis and <i>in vitro</i> Study as Potential Substrates for Indoleamine 2,3-Dioxygenase

Indoleamine 2,3-dioxygenase (hIDO) is an enzyme that catalyzes the oxidative cleavage of the indole ring of l-tryptophan through the kynurenine pathway, thereby exerting immunosuppressive properties in inflammatory and tumoral tissues. The syntheses of 1-(2-fluoroethyl)-tryptophan (1-FETrp) and 1-((1-(2-fluoroethyl)-1<i>H</i>-1,2,3-triazol-4-yl)­methyl)-tryptophan, two <i>N</i>¹-fluoroalkylated tryptophan derivatives, are described here. <i>In vitro</i> enzymatic assays with these two new potential substrates of hIDO show that 1-FETrp is a good and specific substrate of hIDO. Therefore, its radioactive isotopomer, 1-[¹⁸F]­FETrp, should be a molecule of choice to visualize tumoral and inflammatory tissues and/or to validate new potential inhibitors

Query A and query B used for computational similarity search.

<p>Query A and query B used for computational similarity search.</p

New inhibitors of PBPs from resistant bacteria.^a

a<p>The data represent mean values of three independent experiments. Standard deviations were within ±10% of these mean values. RA = residual activity of the enzyme at 1 mM inhibitor, unless stated otherwise. IC₅₀-values were determined in the presence of 0.01% Triton X-100. ^bResidual activity of the enzyme at 500 µM inhibitor.</p

Docking of the anthranilic acid derivative inhibitor 9.

<p>Inhibitor <b>9</b> (magenta) docked into the active site of PBP2x 5204. The amino acids that form interactions with inhibitor <b>9</b> are shown as green sticks.</p

<i>In-vitro</i> antibacterial activities of inhibitors of PBPs from resistant species.

<p><i>In-vitro</i> antibacterial activities of inhibitors of PBPs from resistant species.</p

Synthesis of inhibitor 1.

<p>Synthesis of inhibitor 1.</p

Sequence identity between PBP2x Sp328 and PBP2x 5204.

<p>PBP2x Sp328 and PBP2x 5204 show high sequence identity with differences in only few places.</p

Docking of the sulfonamide inhibitor 1.

<p>Inhibitor <b>1</b> (magenta) docked into the active site of PBP2a (pdb code 1vqq). The amino acids that form interactions with inhibitor <b>1</b> are shown as green sticks.</p

Structures of compounds 1–12.

<p>Structures of compounds 1–12.</p