Molecular modeling studies of 1,2,4-triazine derivatives as novel h-DAAO inhibitors by 3D-QSAR, docking and dynamics simulations.

Human d-amino acid oxidase (h-DAAO) can effectively act on d-serine, which has been actively explored as a novel therapeutic target for treating schizophrenia. In this study, 37 h-DAAO inhibitors based on a 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione scaffold were obtained to construct the optimal comparative molecular field analysis (CoMFA, q 2 = 0.613, r 2 = 0.966) and comparative molecular similarity index analysis (CoMSIA, q 2 = 0.669, r 2 = 0.985) models. The results indicate that the models have good predictability and strong stability. Furthermore, contour maps of the three-dimensional quantitative structure-activity relationship (3D-QSAR) revealed the relationships between the structural features and inhibitory activity. A total of nine new h-DAAO inhibitors were designed, which exhibited good predicted pIC50 values. Through molecular docking and molecular dynamics simulation, four essential residues (i.e., Gly313, Arg283, Tyr224 and Tyr228) were considered to interact with the inhibitor. The hydrogen bonds produced by the triazine structure with protein and the hydrophobic interactions with the residues (i.e., Leu51, His217, Gln53 and Leu215) play an important role in the stability of the inhibitor at the binding site of the protein. Additionally, the compounds D1, D3 and D8, with higher predicted activities, were selected by ADME and bioavailability prediction. The present study could offer a reliable theoretical basis for future structural optimisation, design and synthesis of effective antipsychotics.

Layered double hydroxides as efficient photocatalysts for visible-light degradation of Rhodamine B.

A series of Zn/M-NO3-LDHs (M=Al, Fe, Ti, and Fe/Ti) have been synthesized by two different methods, and their activities for visible-light photocatalytic degradation on Rhodamine B (RB) were tested. Solids were analyzed by XRD, FT-IR, and ICP characterization, confirming the formation of pure LDH phase with good crystal structure. It was observed that the band gap of these nitrate LDH materials was following this order: Zn/Fe-NO3-LDHs (2.55 eV)>Zn/Fe/Ti-NO3-LDHs (2.88 eV)>Zn/Ti-NO3-LDHs (3.0 3eV)>Zn/Al-NO3-LDHs (3.23 eV); however, the degradation performance of RB by four materials followed the order: Zn/Ti-NO3-LDHs (98%)>Zn/Al-NO3-LDHs (96%)>Zn/Fe/Ti-NO3-LDHs (88%)>Zn/Fe-NO3-LDHs (72%). In addition, a possible mechanism for photocatalytic degradation on RB has also been presumed. Moreover, after three regeneration cycles, the percentage of RB degradation rate was still close to 90%.

[Expression changes of nitric oxide synthase mRNA of hypothalamus after sleep deprivation in rats].

OBJECTIVE: To study the effects of rapid eye movement sleep (REMS) deprivation on the expression of mRNA coding for neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) of hypothalamus in rats. METHOD: Flower pot technique was adopted to deprive the REMS of Sprague-Dawley rats for 24 h, 48 h and 72 h respectively. The expression of mRNA coding for nNOS or iNOS of hypothalamus in rats was assayed by reverse-transcription polymerase chain reaction (RT-PCR). RESULT: The amount of nNOS mRNA was significantly higher in 24 h REMS deprivation group (P<0.01), then the amount was lowered in 48 h deprivation group and became significantly lower in 72 h deprivation group than that in the control group (P<0.05). There was low expression of iNOS mRNA of hypothalamus in rats, and there was no difference in the expression of iNOS mRNA among 24 h, 48 h REMS deprivation and the control groups. But the expression was significantly increased in 72 h REMS deprivation group (P<0.01). CONCLUSION: Deprivation of REMS increased the expression of nNOS and iNOS mRNA of hypothalamus. Excessive nitric oxide (NO) might be a major factor resulting in not only the sleep rebound phenomenon but also the injury of human function caused by sleep loss directly or indirectly by other sleep factors.