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• A BFS estimation algorithm based on mixed moment is proposed. • Computation time of proposed algorithm is much less than typical algorithms. • Errors estimated by proposed algorithm and pseudo-Voigt fit are very similar. • No initial guesses, iterations and convergence criterion are needed. • Proposed algorithm is more accurate than quadratic fit and cross-correlation. To estimate Brillouin frequency shift with high accuracy and less computational burden, the mixed moment is used to estimate it for the distributed optical fiber sensor. Its computational burden is much less than that of the typical algorithms. Meanwhile, it is free of curve fitting and initialization of fitting parameters. The optimal order in the proposed algorithm is determined. The accuracy and computation time of the proposed algorithm, the typical spectrum fitting algorithms based on the pseudo-Voigt model, the quadratic polynomials, and the cross-correlation algorithm are compared for the simulated and collected Brillouin spectra with different signal-to-noise ratios. The results reveal that the computation time of the proposed algorithm is only 1/6464–1/3986, 1/33–1/24, 1/111–1/72 of that of the other three algorithms. However, its accuracy is close to that of the spectrum fitting algorithm based on the pseudo-Voigt profile and is a little higher than that of the other two algorithms. [ABSTRACT FROM AUTHOR]

Graphical abstract A series of oxadiazole-based S1P 1 direct-acting agonists, with high affinity for S1P 1 receptor and favorable selectivity against S1P 3 receptor was designed, synthesized and evaluated in vitro and vivo. Highlights • Oxadiazole-based derivatives were designed and progressively modified as S1P 1 agonists. • The agonism activities of compounds for S1P 1 and S1P 3 receptor were evaluated. • Most compounds show excellent activity and selectivity, particularly for 16-3b and 16 - 3g. • In vivo pharmacological, pharmacokinetics and druggability profiles were studied. • The binding mode between 16-3b and the activated S1P 1 model was also reviewed. Abstract Agonism of S1P 1 receptor has been proven to be responsible for peripheral blood lymphopenia and elicts the identification of various S1P 1 modulators. In this paper we described a series of oxadiazole-based S1P 1 direct-acting agonists disubstituted on terminal benzene ring, with high potency for S1P 1 receptor and favorable selectivity against S1P 3 receptor. In addition, two representative agents named 16-3b and 16 - 3g demonstrated impressive efficacy in lymphocyte reduction along with reduced effect on heart rate when orally administered. Furthermore, these compounds have been shown to possess desired pharmacokinetic (PK) and physicochemical profiles. The binding mode between 16 - 3b and the activated S1P 1 model was also studied. [ABSTRACT FROM AUTHOR]

Abstract Flavonoids are a class of polyphenol antioxygen, despite various known biological activities and therapeutic potential, scattered but not much is known about their interactions with drug transporters. P-glycoprotein (P-gp) as a cellular defense mechanism by effluxing its substrates has been widely investigated. The aim of this study was to investigate the inhibitory effects of 75 flavonoids on P-gp in vitro and in vivo and to illuminate the structure–activity relationships of flavonoids with P-gp. Five flavonoids, including tangeretin, sinensetin, isosinensetin, sciadopitysin and oroxylin A exhibited significant inhibition on P-gp in MDR1-MDCKIIcells, which reduced the P-gp-mediated efflux of paraquat and taxol and consequently increased their cell toxicity. In addition, co-administration of digoxin with five flavonoids increased the AUC 0−t of digoxin in different extents in rats, from 19.84% to 81.51%. Molecular docking assays elucidated the inhibitory effect of flavonoids might be related to Pi interactions, but not hydrogen bonds. The pharmacophore model suggested the hydrophobic groups in B benzene ring may play a vital role in the potency of flavonoids inhibition on P-gp. Taken together, our findings would provide the basis for a reliable assessment of the potential risks of flavonoid-containing food/herb–drug interactions in humans. Highlights • Regulation on P-glycoprotein by 75 flavonoids was systematically evaluated. • The inhibitory effects were assessed in cell toxicity and rat pharmacokinetics study. • The potential inhibitory mechanism was elucidated by molecular docking assays. • Structure–activity relationships model was established to design novel inhibitors. [ABSTRACT FROM AUTHOR]