A number of novel NAD(P)H:quinone oxidoreductase 1 (NQO1) inhibitors were discovered from the ChmeDiv database via a simple protocol. Based on two reference NQO1 inhibitors, dicoumarol (DIC) and ES936, shape-based similarity search and cascade docking filtering were conducted to identify new NQO1 inhibitors. Using these techniques, 43 compounds were selected, ordered, and tested. Among them, 7 compounds with novel chemical scaffolds were confirmed to be active by in vitro assays. Determination of the ability for protecting against NQO1-mediated toxicity of β-lapachone (β-lap) confirmed that compounds 8, 10 and 13 may be pharmacological useful for probing the function of NQO1 in cells. Fig. 1 Representative structures of known inhibitors of NQO1.Fig. 10 A549 cells were treated for 2 h with β-lap and 30 µmol•L -1 of the compounds. The toxicity was determined 72 h later by the MTT assay.

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A non-intrusive speech quality assessment method for complex environments was proposed. In the proposed approach, a new sparse representation-based speech reconstruction algorithm was presented to acquire the quasi-clean speech from the noisy degraded signal. Firstly, an over-complete dictionary of the clean speech power spectrum was learned by the K-singular value decomposition algorithm. Then in the sparse representation stage, the stopping residue error was adaptively achieved according to the estimated cross-correlation and the noise spectrum which was adjusted by a posteriori SNR-weighted factor, and the orthogonal matching pursuit approach was applied to reconstruct the clean speech spectrum from the noisy speech. The quasi-clean speech was considered as the reference to a modified PESQ perceptual model, and the mean opinion score of the noisy degraded speech was achieved via the distortions estimation between the quasi-clean speech and the degraded speech. Experimental results show that the proposed approach obtains a correlation coefficient of 0.925 on NOIZEUS complex environment database, which is 99% similar to the performance of the intrusive standard ITU-T PESQ, and 7.1% outperforms non-intrusive standard ITU-T P.563.

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Based on the SAR (structure activity relationship) of TZDs (thiazolidinediones), 3-methyl-1-phenyl-2-pyrazoline-5-one was selected as a substitute for TZD. Compounds of 3-methyl-1-phenyl-4-{4-[(5-methyl-2-phenyloxazol-4-yl)methoxy]benzylene(benzyl)}-2-pyrazol-5-one were designed and synthesized to find some more hypoglycemic active agents and further investigate the SAR of this class of compounds. Butanedione monoxime reacted with (substituted) benzaldehyde via cyclization and chlorination to give 4-(chloromethyl)-5-methyl-2-phenyloxazole derivatives, which condensed with 4-hydroxybenzaldehyde or vanillin, and was followed by the Knoevenagel reaction with 3-methyl-1-phenyl-2-pyrazol-5-one to give compounds Ia-Ih. Compounds Ia-Ih were hydrogenated with Pd-C to give IIa-IIh, and their hypoglycemic activity was evaluated with a glucose oxidase kit and insulin load test on normal mice. Sixteen new target compounds were synthesized. All the compounds were characterized by 1 H NMR, IR, MS and elemental analysis. The preliminary pharmacological tests show that the compounds have good hypoglycemic activity and can enhance the action of insulin, especially Ib, Id and If.