Title: Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from Alangium chinense Hu XY, Zhu SJ, Meng XH, Yu HF, Liu X, Zhang LY, Wei Y, Lei CW, Wei X, Zhou Y Ref: J Org Chem, :, 2022 : PubMed
Unlike reported pyridine hybrids, 2S (1a) and 2R-alanginenmine A (1b) from Alangium chinense featuring an unprecedented piperidine-bridged polypyridine skeleton represented a pair of alkaloid subtypes with a unique multiple pyridine scaffold. Enlightened by the rare structural characteristics and possible biosynthetic pathway, (+/-)-alanginenmine A (1) have been achieved in ideal yield by gram-class total synthesis with four steps. In addition, both compounds 1a and 1b exhibited anti-acetylcholinesterase (AChE) and HIV-1 protease activities in the biological activity evaluation. Further, molecular docking was investigated for the mechanism of action between the isolated compounds and HIV-1 protease. The stronger Coulomb interactions and van der Waals interaction, as well as the hydrogen bond interactions of 1a, might be the main cause for its better anti-HIV-1 protease activity than 1b. This work provided a comprehensive research including natural product discovery, bioactivity evaluation, and total synthesis for the new type of leading anti-HIV-1 protease.
Development of potent biocatalysts for enzymatic detoxification of estrogenic mycotoxin zearalenone (ZEN) and its more toxic derivative alpha-zearalenol (alpha-ZOL) is of great interest. Here, we report the crystal structures of a ZEN-hydrolyzing enzyme from Rhinocladiella mackenziei (RmZHD), including substrate complexes. A molecular mechanism for the distinct activity of RmZHD in hydrolyzing the structurally similar ZEN and alpha-ZOL is then proposed. In addition, structure-based engineering to modify the substrate-binding pocket and improve the RmZHD activity toward alpha-ZOL is presented. These results expand our scope in understanding the catalytic mechanism of ZHD-family enzymes and are of vital importance in further industrial applications.
Title: Improved prescription of taohechengqi-tang alleviates D-galactosamine acute liver failure in rats Zhang Y, Luo JX, Hu XY, Yang F, Zhong S, Lin W Ref: World J Gastroenterol, 22:2558, 2016 : PubMed
AIM: To investigate the hepatoprotective effect of improved prescription of Taohechengqi-tang (IPTT) against acute liver failure (ALF) in rats. METHODS: Seventy specific pathogen free male Wistar rats were randomly divided into four groups: control group (normal rats, n = 10), ALF group (ALF model, n = 20), Stronger Neo-Minophagen C (SNMC) group (ALF model + SNMC, n = 20), and IPTT group (ALF model + IPTT, n = 20). The ALF model group was administered an intraperitoneal injection of D-galactosamine (1.4 g/kg), and the control group received normal saline intraperitoneally. The SNMC and IPTT groups were treated with SMMC (15.6 mg/kg) or IPTT (28.6 g/kg) by gavage at 24 h intervals, and the ALF and control groups were treated with normal saline. At 36 h after injection, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, and cholinesterase and prothrombin time were determined, and liver histopathological scores were observed by microscopy after hematoxylin and eosin staining. mRNA expression of high mobility group box (HMGB) 1, toll-like receptor (TLR) 4, nuclear factor kappa B (NF-kappaB) and caspase-3 were analyzed via fluorescence quantitative reverse transcriptase polymerase chain reaction. Proliferating cell nuclear antigen (PCNA) immunohistochemistry in liver tissue was also performed. RESULTS: D-galactosamine notably decreased the biochemical and coagulation profiles in serum. IPTT not only improved liver function and histopathology but also normalized the gene expression levels in liver tissue. Compared with the model group, in the IPTT and SNMC groups, HMGB1 mRNA/beta-actin (0.06 +/- 0.03, 0.11 +/- 0.04 vs 0.25 +/- 0.04, P < 0.05); TLR4 mRNA/beta-actin (0.07 +/- 0.02, 0.22 +/- 0.08 vs 0.41 +/- 0.22, P < 0.05); NF-kappaB mRNA/beta-actin (0.74 +/- 0.41, 1.78 +/- 0.64 vs 2.68 +/- 1.35, P < 0.05); and caspase-3 mRNA/beta-actin levels were all significantly reduced (1.61 +/- 0.45, 2.57 +/- 1.04 vs 3.41 +/- 0.85, P < 0.05). The gene expression levels were significantly lower in the IPTT group than in the SNMC group (P < 0.05). Compared with the model group, the PCNA expression in liver tissue was significantly enhanced in the IPTT and SNMC groups (36.34 +/- 4.91, 25.57 +/- 2.94 vs 17.55 +/- 2.40, P < 0.05). CONCLUSION: IPTT attenuates inflammation in ALF via inhibition of HMGB1 production, which may contribute to limited liver regeneration.
