Thirteen PRDX4 Truth And Lies Revealed

The binding affinities inferred from the data were 671 > 672 > 670 > 669. The LC/MS functional assay was then used to measure the extent of inhibition each compound displayed. The compounds were tested at varying concentrations, ranging from 0.05 ��M to 1 ��M, with 1 ��M MtSK and 2 ��M shikimic acid. The amount of S3P formed was measured at each concentration, and EC50 values were determined. All four of the compounds showed complete inhibition at 1 ��M of inhibitor. The EC50 Bleomycin cell line values for compounds 669, 670, 671, and 672 were determined to be 0.03, 0.24, 0.07, and 0.18 ��M, respectively (Fig. 5).31 Figure 5 Staurosporine, compound 669. The pyrazolone analogs displayed MtSK inhibition at IC50 values lower than 1 ��M.31 Based on the structure�Cactivity relationship in the series, the phenyl sulfonamide portion of the molecule is required for the activity, and a single substitution of a halogen at the Para position of the phenyl enhances the MtSK inhibition as for compound 671 (Fig. 6). Figure 6 Pyrazolone analogs. Oxadiazole-amides and 2-aminobenzothiazoles A total of 404 antitubercular compounds from the National Institute of Allergy and Infectious Diseases (NIAID) were tested in vitro using a LC/MS functional assay, of which PRDX4 14 compounds displayed inhibition of MtSK by >90%. IC50 values (Table 6) were determined for these 14 compounds with the lowest IC50 = 1.94 �� 0.06 for compound 686. Table 6 Chemical structure of oxadiazole-amides and 2-aminobenzothiazoles. In all, 10 of the 14 compounds, compounds 673�C682, contain an oxadiazole-amide scaffold, while the remaining four compounds, compounds 683�C686, contain a 2-aminobenzothiazole scaffold. Ligand docking, using Schrodinger software, was performed to determine the interactions between the different ligand scaffolds and the MtSK crystal structure (PDB code 2DFT, conformer B). Compounds containing the oxadiazole-amide structure interact with residues V35, R58 (NMP-binding domain), P118, and L119 (lid). Compounds containing Duvelisib the 2-aminobenzothiazole structure displays interactions with P11 (P-loop), V35, I37, I45, F57 (NMP-binding domain), and R136.34 All oxadiazole-amides and 2-aminobenzothiazoles in this series have H37Rv IC90 values below 5 ��g/mL and SI values well over the threshold of 10.29 Based on molecular modeling described in Table 5 containing MtSK inhibitors, most compounds 675, 679, and 686 displayed IC50 values of �� 5 ��M. Compounds 675 and 679 contain the 2,5-disubstituted-1,3, 4-oxadiazole system. Both compounds contain, as required, structural features, a phenyl at the 5-position of the oxadiazole ring and at the other end, the carboxamide is linked to a substituted phenyl.