Barefootlau8772

through MMPB/GBSA methods that complements the compound affinity for the said target. In a nutshell, the identified hit could be subjected to structure, biological and pharmacokinetic optimization for development of effective FabH inhibitors.This study aims to determine whether atomoxetine (ATX), used as an alternative to methylphenidate, affects superoxide dismutase (SOD) activity besides glutathione (GSH) and malondialdehyde (MDA) levels, apart from determining possible effects of ATX on SOD activity through molecular docking studies. 24 male Wistar rats were divided into 4 groups, each containing 6 members. After a 6-week application of ATX, blood samples and brain tissues were obtained from the rats for biochemical analyses. Besides, molecular docking studies were conducted using PyRx and Discovery Studio 3.0 programs. No significant difference occurred in GSH and MDA levels after ATX application. A high-dose application of ATX caused a statistically significant change only in the serum-SOD activity compared to that of Control Group. Molecular docking studies revealed that ATX settled in the biggest space rather than the catalytic regions of Cu2Zn2-SOD. Our biochemical and molecular docking data showed that ATX, an alternative drug to stimulant methylphenidate, showed no significant changes in the antioxidant defence system at either low or therapeutic doses after long-term use. Therefore, we suggest ATX could be used as a substitute for methylphenidate in the long-term treatment of ADHD.In this paper, based on molecular hybridization, a series of [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing hydrazine was synthesized and their antiproliferative activities against 5 cancer cell lines (MGC-803, PC3, PC9, EC9706 and SMMC-7721) were evaluated. We found that most of them exhibited obvious growth inhibition effects on these tested cancer cells, especially compound 34 on PC3 cells (IC50 = 26.25 ± 0.28 nM). Meanwhile, compound 34 displayed best selectivity on PC3, compared with the other cancer cell lines, as well as excellent selectivity towards normal cell lines (Het-1A, L02 and GES-1). Further investigations demonstrated that 34 could significantly inhibit PC3 cells' colony formation, increase cellular ROS content, suppress EGFR expression and induce apoptosis. Our findings indicate that 34 may serve as a novel lead compound for the discovery of more triazolopyrimidine derivatives with improved anticancer potency and selectivity.The development of NSAIDs/iNOS inhibitor hybrids is a new strategy for the treatment of inflammatory diseases by suppression of the overproduction of PGE2 and NO. A novel series of aryl carboximidamides 4a-g and their cyclized 3-aryl-1,2,4-oxadiazoles 5a-g counterparts derived from indomethacin 1 were synthesized. Most of the target compounds displayed lower LPS-induced NO production IC50 in RAW 264.7 cells and potent in vitro iNOS and PGE2 inhibitory activity than indomethacin. Moreover, in carrageenan-induced rat paw oedema method, most of them exhibited higher in vivo anti-inflammatory activity than the reference drug indomethacin. Notably, 4 hrs after carrageenan injection, compound 4a proved to be the most potent anti-inflammatory agent in this study, with almost two- and eight-fold more active than the reference drugs indomethacin (1) and celecoxib, respectively. Compound 4a proved to be inhibitor to LPS-induced NO production, iNOS activity and PGE2 with IC50 of 10.70 μM, 2.31 μM, and 29 nM; respectively. Compounds 4a and 5b possessed the lowest ulcerogenic liabilities (35% and 38%, respectively) compared to 1. Histopathological analysis revealed that compounds 4a and 5b demonstrated reduced degeneration and healing of ulcers. Molecular docking studies into the catalytic binding pocket of the iNOS protein receptor (PDB ID 1r35) showed good correlation with the obtained biological results. Parameters of Lipinski's rule of five and ADMET analysis were calculated where compound 4a had reasonable drug-likeness with acceptable physicochemical properties so it could be used as promising orally absorbed anti-inflammatory therapy and entitled to be used as future template for further investigations.The bioactive peptides and trace element selenium (Se) both have good antioxidant activity. However, whether combined Se and bioactive peptides have more excellent antioxidant activity remain unknown. The aim of this study is to prepare a Se-rich peptide fraction containing both Se and peptides from Se-rich yeast protein hydrolysate and investigated its antioxidant activity and effect on ultraviolet B (UVB) radiation-induced skin oxidative damage. The peptide fractions with different molecular weight (MW) and Se content were obtained by enzymatically hydrolyzing normal or Se-rich yeast proteins followed by a filtration process. see more In vitro free radical scavenging and lipid peroxidation inhibition assays showed that Se-rich peptides fraction with lower MW of less then 1 kDa (sSeP) had the highest antioxidant activity compared with Se-rich peptide fractions with higher MW of less then 3 kDa or normal peptide fractions. Oral administration of sSeP significantly decreased the level of malonaldehyde (MDA) in liver and serum, and increased the activity of glutathione peroxidase (GPx) in liver and serum in normal mice. When topically applied on the dorsal skin of mice, sSeP effectively alleviate UVB radiation-induced skin damage and oxidative stress by increasing GPx and catalase activities and glutathione content in skin or serum. Furthermore, sSeP showed a protective effect against H2O2-induced cytotoxicity in cultured human epidermal keratinocytes (HaCaT) cells probably by increasing aquaporin-3 expression and attenuating the phosphorylation of p38 MAPK. Overall, the results showed that Se-rich yeast peptide fraction containing Se and bioactive peptides could be a promising antioxidant nutrient used as food additive to enhance the body's antioxidant ability or as cosmeceutical product to minimize the skin oxidative damage.Natural products with antioxidant and anti-inflammatory properties are important sources of therapeutic agents. The nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is a well-known defense system against oxidative stress. In this study, a panel of extracts of plants, fungi, and bacteria were screened for Nrf2 activation in a cell-based assay and a crude extract of cultured marine Streptomyces sp. YP127 was found to activate Nrf2. Chemical investigation of the extracts led to isolation of a series of napyradiomycins that activate Nrf2. Among them, napyradiomycin, 16Z-19-hydroxynapyradiomycin A1 (1) exhibited the highest Nrf2-activating efficacy. Compound 1 was further confirmed to induce both mRNA and protein levels of Nrf2-dependent antioxidant enzyme genes in BV-2 microglial cells and suppress inflammatory mediators and intracellular reactive oxygen species. Our findings confirm the antioxidant and anti-inflammatory properties of compound 1, making it a promising therapeutic natural compound for various diseases associated with oxidative stress and inflammation.