Design and synthesis of novel JNK inhibitors targeting liver pyruvate kinase for the treatment of non-alcoholic fatty liver disease and hepatocellular carcinoma.

Non-alcoholic fatty liver disease (NAFLD) comprises a broad range of liver disease including hepatocellular carcinoma (HCC) with is no FDA-approved drug. Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP generation in liver presenting a potential target for the treatment of NAFLD. Based on our recent finding of JNK-5A's effectiveness in inhibiting PKLR expression through a drug repositioning pipeline, this study aims to improve its efficacy further.

Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase.

Liver pyruvate kinase (PKL) has recently emerged as a new target for non-alcoholic fatty liver disease (NAFLD), and inhibitors of this enzyme could represent a new therapeutic option. However, this breakthrough is complicated by selectivity issues since pyruvate kinase exists in four different isoforms. In this work, we report that ellagic acid (EA) and its derivatives, present in numerous fruits and vegetables, can inhibit PKL potently and selectively.

Discovery of therapeutic agents targeting PKLR for NAFLD using drug repositioning.

Background: Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver pathologies. However, no medical treatment has been approved for the treatment of NAFLD. In our previous study, we found that PKLR could be a potential target for treatment of NALFD.

Unexpected synthesis of novel 2-pyrone derivatives: crystal structures, Hirshfeld surface analysis and computational studies.

Here we report synthesis of three new compounds namely, 1-acetyl-1H-benzimidazolo-2(3H)-one (), -(5-acetyl-6-methyl-2-oxo-2H-pyran-4-yl)--(2-acetamidophenyl)acetamide () and -(2-acetamidophenyl)--2-oxo-2H-pyran-4-yl)acetamide () have been synthesized and characterized by single crystal X-ray diffraction. Compounds and crystallize in the monoclinic space groups P21/n, and P21/c, respectively, while crystallizes in the triclinic space group P-1. The theoretical parameters of - have been calculated through density functional theory (DFT) by using the hybrid functional B3LYP and basis set 6-311++G**.

Crystal structure, computational study and Hirshfeld surface analysis of ethyl (2,3)-3-(3-amino-1-1,2,4-triazol-1-yl)-2-hy-droxy-3-phenyl-propano-ate.

In the title mol-ecule, CHNO, the mean planes of the phenyl and triazole rings are nearly perpendicular to one another as a result of the intra-molecular C-H⋯O and C-H⋯π(ring) inter-actions. In the crystal, layers parallel to (101) are generated by O-H⋯N, N-H⋯O and N-H⋯N hydrogen bonds. The layers are connected by inversion-related pairs of C-H⋯O hydrogen bonds.

A newly synthesized 6-methyl-7,8,9-[1,2,4]triazolo[4,3-][1,2,4]triazepin-8-one for potential inhibitor of adenosine A1 receptor: a combined experimental and computational studies.

6-Methyl-7,8,9-[1,2,4]triazolo[4,3-][1,2,4]triazepin-8-onehas been synthesized, characterized by spectroscopic techniques (FT-IR, H and C NMR) and finally the structure was confirmed by single crystal X-ray diffraction studies. In the title molecule, CHNO, the 7-membered ring adopts a bowl-like conformation. In the crystal, the molecules form stacks along the -axis direction through offset π-stacking interactions between the 5-membered rings and C-H···N hydrogen bonds.

Crystal structure, DFT study and Hirshfeld surface analysis of 1-nonyl-2,3-di-hydro-1-indole-2,3-dione.

In the title mol-ecule, CHNO, the di-hydro-indole portion is planar (r.m.s.