Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models.

In spinocerebellar ataxia type 17 (SCA17), the expansion of a translated CAG repeat in the TATA box binding protein (TBP) gene results in a long polyglutamine (polyQ) tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP) expression to test indole and synthetic derivative NC001-8 for neuroprotection.

Molecular iodine-mediated reaction of 2-(2-phenylethynyl)-Morita-Baylis-Hillman adducts: an easy route to naphthyl ketones and iodo-substituted isochromenes.

The molecular iodine-promoted reaction of 2-(2-phenylethynyl)-Morita-Baylis-Hillman adducts is reported. In the presence of I2, naphthyl ketone derivatives are produced, whereas in the presence of I2/K3PO4, iodo-substituted isochromene derivatives are produced.

The potential of indole and a synthetic derivative for polyQ aggregation reduction by enhancement of the chaperone and autophagy systems.

In polyglutamine (polyQ)-mediated disorders, the expansion of translated CAG repeats in the disease genes result in long polyQ tracts in their respective proteins, leading to intracellular accumulation of aggregated polyQ proteins, production of reactive oxygen species, and cell death. The molecular chaperones act in preventing protein misfolding and aggregation, thus inhibiting a wide range of harmful downstream events. In the circumstance of accumulation of aggregated polyQ proteins, the autophagic pathway is induced to degrade the misfolded or aggregated proteins.

Synthesis of indolylquinolines, indolylacridines, and indolylcyclopenta[b]quinolines from the Baylis-Hillman adducts: an in situ [1,3]-sigmatropic rearrangement of an indole nucleus to access indolylacridines and indolylcyclopenta[b]quinolines.

A simple and easy route to the synthesis of a variety of structurally diverse indolylquinolines, indolylacridines, and indolylcyclopenta[b]quinoline derivatives via the reductive cyclization of C-alkylated indole derivatives, derived from acyclic as well as cyclic Baylis-Hillman adducts with indoles, is described. An unusual in situ [1,3]-sigmatropic rearrangement of the indole nucleus was observed during the reductive cyclicization of α-regioselective B-H adducts containing indoles to produce indolylacridines and indolylcyclopenta[b]quinoline derivatives.

Alcohol mediated synthesis of 4-oxo-2-aryl-4H-chromene-3-carboxylate derivatives from 4-hydroxycoumarins.

The unusual alcohol mediated formation of 4-oxo-2-aryl-4H-chromene-3-carboxylate (flavone-3-carboxylate) derivatives from 4-hydroxycoumarins and β-nitroalkenes in an alcoholic medium is described. The transformation occurs via the in situ formation of a Michael adduct, followed by the alkoxide ion mediated rearrangement of the intermediate. The effect of the different alcohol and nonalcohol media on the reaction was investigated.