Antiausterity Agents from <i>Uvaria dac</i> and Their Preferential Cytotoxic Activity against Human Pancreatic Cancer Cell Lines in a Nutrient-Deprived Condition

Human pancreatic cancer cell lines are known for their inherent tolerance to nutrition starvation, which enables them to survive under a hypovascular (austerity) tumor microenvironment. The search for agents that preferentially retard the survival of cancer cells under low nutrition conditions (antiausterity agent) is a novel approach to anticancer drug discovery. In this study, it was found that a dichloromethane extract of the stem of <i>Uvaria dac</i> preferentially inhibited PANC-1 human pancreatic cancer cells survival under nutrition-deprived conditions at a concentration of 10 μg/mL. Workup of this bioactive extract led to the discovery of (+)-grandifloracin (<b>8</b>) as a potent antiausterity agent as evaluated in a panel of four human pancreatic cancer cell lines, PANC-1 (PC₅₀, 14.5 μM), PSN-1 (PC₅₀, 32.6 μM), MIA PaCa-2 (PC₅₀, 17.5 μM), and KLM-1 (32.7 μM). (+)-Grandifloracin (<b>8</b>) has been isolated from a natural source for the first time. Its absolute stereochemistry was established by single-crystal X-ray crystallography and circular dichroism spectroscopic analysis. In addition to this, seven other new highly oxygenated cyclohexene derivatives, named uvaridacanes A (<b>1</b>) and B (<b>2</b>), uvaridacols A–D (<b>3</b>, <b>4</b>,<b> 6</b>, <b>7</b>), and uvaridapoxide A (<b>5</b>), were also isolated and structurally characterized

Synthesis, characterization and antimicrobial activity of a bidentate NS Schiff base of <i>S</i>-benzyl dithiocarbazate and its divalent complexes

<p>The reaction of S-benzyl dithiocarbazate (SBDTC) with 2,4,5-trimethoxybenzaldehyde afforded a bidentate NS Schiff base <b>1</b> (benzyl-3-<i>N</i>-(2,4,5-trimethoxyphenylmethylenehydrazine carbodithioate), which on further reaction with M(II) (where M(II) = nickel(II), zinc(II), palladium(II) and copper(II)) in ethanol under reflux yielded bis-chelated inner complexes [ML₂] <b>2</b>–<b>5</b> with deprotonated L. The ligand and its complexes were characterized by physicochemical techniques, <i>viz.</i>, molar conductance, magnetic susceptibility measurement, IR, NMR, UV–Vis and mass spectroscopic techniques. The crystal structures of <b>1</b> and <b>5</b> were also determined by single-crystal X-ray crystallography. The crystal structure analysis showed that the ligand exists in its thione tautomeric form. In the complexes, each of the two deprotonated ligands chelated the metal ions through the <i>β</i>-nitrogen and the thione sulfur forming five-membered rings. The copper(II) complex (<b>5</b>) exhibited a square-planar geometry, where the two N₂S₂ chromophores are arranged <i>trans</i>. All the compounds showed strong antibacterial activity against <i>S.</i>-<i>β</i>-<i>hemolyticus</i>, <i>Klebsiella pneumoni</i>, and <i>Escherichia coli</i>. The compounds also showed strong antifungal activity against <i>Aspergillus fumigatus</i>, <i>Aspergillus niger</i>, <i>Aspergillus flavus</i>, and <i>Candida albicans</i> with the exception of the palladium(II) complex (<b>4</b>) which showed no activity, while all the compounds showed no activity against <i>Fusarium vasinfectum</i>.</p