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Promoting energy metabolism is known to provide therapeutic effects for obesity and associated metabolic disorders. The present study evaluated the therapeutic effects of the newly identified bouchardatine (Bou) on obesity-associated metabolic disorders and the molecular mechanisms of these effects.The molecular mode of action of Bou for its effects on lipid metabolism was first examined in 3T3-L1 adipocytes and HepG2 cells. This was followed by an evaluation of its metabolic effects in mice fed a high-fat diet for 16 weeks with Bou being administered in the last 5 weeks. Further mechanistic investigations were conducted in pertinent organs of the mice and relevant cell models.In 3T3-L1 adipocytes, Bou reduced lipid content and increased sirtuin 1 (SIRT1) activity to facilitate liver kinase B1 (LKB1) activation of AMPK. Chronic administration of Bou (50 mg∙kgBou may have therapeutic potential for obesity-related metabolic diseases by increasing the capacity of energy expenditure in adipose tissues and liver through a mechanism involving the SIRT1-LKB1-AMPK axis.

The reaction of CuCl2·2H2O with N-(p-nitrophenyl)-N′-butoxycarbonyl)-thiourea (H2nbt) and N-(o-nitrophenyl)-N′-(ethoxycarbonyl)-thiourea (H2net) gave two copper(I) complexes, [Cu(H2nbt)2Cl]2, 1, and Cu(H2net)2Cl, 2, respectively. In complex 1, the ligand H2nbt is S,S-bonded to two Cu atoms, and the two ligand molecules exchange “long” CuS interactions ( Cu  S = 2.700 A ) forming a dimer, in which the Cu atom has a distorted tetrahedral coordination ClCuS(1) = 119.9(1),ClCuS(2) = 122.9(1) and S(1)CuS(2) = 108.4(1)° and is 0.387(2) A from th basal S,S,Cl with unequal Cu  S [2.253(3), 2.244(3) A ] and Cu  Cl [2.247(3) A ] bonds. In complex 2, the copper (I) atom is inn a trigonal planar geometry [ClCuS(1) = 120.53(5), ClCuS(2) = 118.43(5) and S(1)CuS(2) = 119.16(5)°] with two unequal Cu  S [2.228(1), 2.232(1) A ] and Cu  Cl [2.251(1) A ] bonds.

Two polyhydroxylated steroids have been isolated from the South China Sea soft coral Sinularia microclavata, and their structures were established as 24-methylenecholestane-1 alpha,3 beta,5 alpha,6 beta-tetrol and 1 alpha,3 beta,5 alpha-trihydroxy-24-methylenecholestan-6-one from spectral evidence and from comparison with two reference compounds, numersterol A and 24-methylenecholestane-1 alpha,3 beta,5 alpha,6 beta, 25-pentol, which were isolated from the soft corals, Simularia numerosa and Sarcophyton glaucum, respectively.

In order to improve the selectivity of 5-N-methyl quindoline (cryptolepine) derivatives as telomeric quadruplex binding ligands versus duplex DNA, a series of peptidyl-benzofuroquinoline (P-BFQ) conjugates (2a-2n) were designed and synthesized. Their interactions with telomeric quadruplex and duplex DNA were examined by using the fluorescence resonance energy transfer (FRET) melting assay, surface plasmon resonance (SPR), circular dichroism spectroscopy (CD), and molecular modeling studies. Introduction of a peptidyl group at 11-position of the aromatic benzofuroquinoline scaffold not only effectively increased its binding affinity, but also significantly improved its selectivity toward telomeric quadruplex versus duplex DNA. Combined with the data for their inhibitory effects on telomerase activity, their structure-activity relationships (SARs) studies showed that the types of amino acid residues and the length of the peptidyl side chains were important for the improvement of their interactions with the telomeric G-quadruplex. Long-term exposure of human cancer cells to 2c showed a remarkable cessation in population growth and cellular senescence phenotype, and accompanied by a shortening of the telomere length. Refereed/Peer-reviewed

A series of 2,4-disubstituted quinazoline derivatives found to be a new type of highly selective ligand to bind with telomeric G-quadruplex DNA, and their biological properties were reported for the first time.Their interactions with telomeric G-quadruplex DNA were evaluated by using fluorescence resonance energy transfer (FRET) melting assay, circular dichroism (CD) spectroscopy, surface plasmon resonance (SPR), nuclear magnetic resonance (NMR), and molecular modeling. Our results showed that these derivatives could well recognize G-quadruplex and have high selectivity toward G-quadruplex over duplex DNA. The structure-activity relationships (SARs) study revealed that the disubstitution of quinazoline and the length of the amide side chain were important for its interaction with the G-quadruplex. Furthermore, telomerase inhibition of the quinazoline derivatives and their cellular effects were studied. Refereed/Peer-reviewed