Here, we have identified the interaction site of the contraceptive drug gamendazole using computational modeling. The drug was previously described as a ligand for eukaryotic translation elongation factor 1-α 1 (eEF1A1) and found to be a potential target site for derivatives of 2-phenyl-3-hydroxy-4(1 H)-quinolinones (3-HQs), which exhibit anticancer activity. The interaction of this class of derivatives of 3-HQs with eEF1A1 inside cancer cells was confirmed via pull-down assay. We designed and synthesized a new family of 3-HQs and subsequently applied isothermal titration calorimetry to show that these compounds strongly bind to eEF1A1. Further, we found that some of these derivatives possess significant in vitro anticancer activity.
Catalytic hydrogenation of 2‐phenyl‐3‐hydroxyquinolin‐4(1H)‐ones afforded their 5,6,7,8‐tetrahydroquinolin‐4(1H)‐one analogues, which gained stability under acidic as well as alkaline conditions. For some 2‐(4‐aminophenyl) derivatives, unusual N‐isopropyl group assembling was observed in various solvents and therefore was studied in more details. The prepared derivatives were studied in context of their fluorescence properties. Some of them retained the dual character of fluorescent spectra as well as quantum yields similar to their non‐reduced parent compounds and thus were studied as potential ratiometric pH indicators.
A s of September 9, 2019, the Editors issue an Expression of Concern to advise readers that an investigation is underway concerning the ITC data (Figure 9, Table 2) as the reported values for ΔH and ΔS are more than 3 order of magnitude greater than is generally accepted to be possible for a small-molecule−protein interaction. The status of this Article will be updated upon the completion of editorial review and the outcome of that investigation.
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