Search

Background: Non-alcoholic fatty liver (NAFLD) and its related metabolic syndrome have become major threats to human health, but there is still a need for effective and safe drugs to treat these conditions. Here we aimed to identify potential drug candidates for NAFLD and the underlying molecular mechanisms. Methods: A drug repositioning strategy was used to screen an FDA-approved drug library with approximately 3000 compounds in an in vitro hepatocyte model of lipid accumulation, with honokiol identified as an effective anti-NAFLD candidate. We systematically examined the therapeutic effect of honokiol in NAFLD and metabolic syndrome in multiple in vitro and in vivo models. Transcriptomic examination and biotin-streptavidin binding assays were used to explore the underlying molecular mechanisms, confirmed by rescue experiments. Results: Honokiol significantly inhibited metabolic syndrome and NAFLD progression as evidenced by improved hepatic steatosis, liver fibrosis, adipose inflammation, and insulin resistance. Mechanistically, the beneficial effects of honokiol were largely through AMPK activation. Rather than acting on the classical upstream regulators of AMPK, honokiol directly bound to the AMPKγ1 subunit to robustly activate AMPK signaling. Mutation of honokiol-binding sites of AMPKγ1 largely abolished the protective capacity of honokiol against NAFLD. Conclusion: These findings clearly demonstrate the beneficial effects of honokiol in multiple models and reveal a previously unappreciated signaling mechanism of honokiol in NAFLD and metabolic syndrome. This study also provides new insights into metabolic disease treatment by targeting AMPKγ1 subunit-mediated signaling activation. [ABSTRACT FROM AUTHOR]

A new diimide derivative, named ( - )-byssochlamic acid bisdiimide (1), was isolated from the mixed broth of two mangrove fungi (strain no. K38 and E33) from the South China sea coast. The structure of 1 was determined by comprehensive spectroscopic methods, including 1D and 2D NMR (COSY, HMQC, and HMBC) and semi-synthesis. Primary bioassays showed that 1 had weak cytotoxic activity against Hep-2 and HepG2 cells. [ABSTRACT FROM AUTHOR]

Abstract: Eleven transition metal complexes of three asymmetrical tridentate thioether ligands, 8-((pyridin-2-yl)methylthio) quinoline (TQMP2), 8-((pyridin-3-yl)methylthio) quinoline (TQMP3), 8-((pyridin-4-yl)methylthio) quinoline (TQMP4) and one symmetrical pentadentate ligand 2,6-bis (8-quinolinylthiomethyl) pyridine (DTQMP) were prepared. The structures of all these complexes were identified by means of elemental analysis (EA), infrared spectra (IR) and single-crystal diffraction, providing three different kinds of basic conformations, (1) discrete mononuclear structures, (2) dinuclear rings and (3) 1D polymer chains. The antibacterial, antifungal and pesticide activities of the four ligands and 11 complexes were also studied. [Copyright &y& Elsevier]

Abstract: The semirigid tridentate 8-(2-pyridinylmethylthio)quinoline ligand (Q1) is shown to form the structurally characterized transition metal complexes [Cu(Q1)Cl2] (1), [Co(Q1)(NO3)2] (2), [Cd(Q1)(NO3)2] (3), [Cd(Q1)I2] (4). [Cu(Q1)2](BF4)2·(H2O)2 (5), [Cu(Q1)2](ClO4)2·(CH3COCH3)2 (6), [Zn(Q1)2](ClO4)2(H2O)2 (7), [Cd2(Q1)2Br4] (8), [Ag2(Q1)2(ClO4)2] (9), and [Ag2(Q1)2(NO3)2] (10). Four types of structures have been observed: ML-type in complexes 1–4, in which the anions Cl−, NO3 − or I− also participate in the coordination; ML 2 − type in complexes 5–7 without direct coordination of the anions BF4 − or ClO4 − and with more (Cu2+) or less (Zn2+) distorted bis-fac coordinated Q1; M 2 L 2 -type in complex 8, in which two Br− ions act as bridges between two metal ions; and M 2 (μ-L) 2-type in complexes 9 and 10, in which the ligand bridges two anion binding and Ag–Ag bonded ions. Depending on electron configuration and size, different coordination patterns are observed with the bonds from the metal ions to Npyridyl longer or shorter than those to Nquinoline. Typically Q1 acts as a facially coordinating tridentate chelate ligand except for the compounds 9 and 10 with low-coordinate silver(I). Except for 6 and 8, the complexes exhibit distinct constraining effects against both G(+) and G(-) bacteria. Complexes 1, 3, 4, 5, 7 have considerable antifungal activities and complexes 1, 5, 7, and 10 show selective effects to restrain certain botanic bacteria. Electrochemical studies show quasi-reversible reduction behavior for the copper(II) complexes 1, 5 and 6. [Copyright &y& Elsevier]

Abstract: A new pyrrolyl 4-quinolinone alkaloid with an unprecedented ring system, named penicinoline (1) was isolated from a mangrove endophytic fungus. The structure of 1 was elucidated by spectroscopic methods and comparison with its derivative, penicinotam (1a), an unexpected lactam that was obtained from 1 by intramolecular dehydration. The structure of 1a was unambiguously confirmed by single-crystal X-ray analysis. Penicinoline (1) showed potent in vitro cytotoxicity toward 95-D and HepG2 cell lines with IC50 values of 0.57 and 6.5μg/mL, respectively. [Copyright &y& Elsevier]