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The enhancement of intracellular stresses such as oxidative stress and endoplasmic reticulum (ER) stress has been implicated in several neurodegenerative disorders including Parkinson's disease (PD). During a search for compounds that regulate ER stress, a dibenzoylmethane (DBM) derivative 14-26 (2,2'-dimethoxydibenzoylmethane) was identified as a novel neuroprotective agent. Analysis in SH-SY5Y cells and in PC12 cells revealed that the regulation of ER stress by 14-26 was associated with its anti-oxidative property. 14-26 prevented the production of reactive oxygen species (ROS) when the cells were exposed to oxidants such as hydrogen peroxide and 6-hydroxydopamine (6-OHDA) or an ER stressor brefeldin A (BFA). 14-26 also prevented ROS-induced damage in both the ER and the mitochondria, including the protein carbonylation in the microsome and the reduction of the mitochondrial membrane potential. Further examination disclosed the presence of the iron-chelating activity in 14-26. In vivo, 14-26 suppressed both oxidative stress and ER stress and prevented neuronal death in the substantia nigra pars compacta (SNpc) after injection of 6-OHDA in mice. These results suggest that 14-26 is an antioxidant that protects dopaminergic neurons against both oxidative stress and ER stress and could be a therapeutic candidate for the treatment of PD. neuronal cell death; stress response; Parkinson's disease

Research has been conducted on the beta-carboline alkaloids. The syntheses of these alkaloids has been performed and the results and the construction of beta-carboline-N-oxides is described.

A novel method for the synthesis of carazostatin, hyellazole and carbazoquinocins was developed based on cross-coupling reactions with 3-iodoindole and vinylstannane. The resulting intermediate produces an alcohol after reacting with ethynylmagnesium bromide followed by etherification. Successive reactions led to the formation of a triflate intermediate which forms carazostatin via palladium-catalyzed reaction.

Grossularines-2 (1b) and -1 (1a), in about 37% yields, are obtained from the reaction of N-deprotected methyl ester with p-(OMOM)phenyllithium or 3-(N-TIPS)indolyllithium, respectively. Reaction of a methyl ester with the same reagents yields 51% of 1b and 63% of 1a. A low yield of 1b is obtained from the reaction of triflate, carbon monoxide and p-(OMOM)phenylboronic acid followed by hydrolysis.

The synthesis of the 3-amino-1,4-dimethyl and 3-amino-1-methyl derivatives of 5H-pyrido(4,3-b)indole (Trp-P-1 and Trp-P-2) proceeds through the thermal electrocyclic reaction of the 1-azahexa-1,3,5-triene system involving the indole (b) bond. N-(benzenesulfonyl)indole provides the 2-vinylindole substrates via a four-step sequence. Trp-P-1 and Trp-P-2 are genotoxic heterocyclic amines produced by the overcooking of protein-containing food.

The synthesis mutagenic heterocyclic amines included a tautomeric process to provide imidazo(4, 5-b)pyridin-5(4H)-ones and a thermal electrocyclic reaction of 2-azahexa-1,3, 5-trienes. The heterocyclic amines were 2-amino-1-methyl-6-phenylimidazo (4, 5-b)pyridine and 2-amino-1,6-dimethylimidazo(4,5-b)pyridine. 1-methyl-2,4, 5-tribromoimidazole formed the starting material in the preparation of the desired 5-alkenyl-4-isocyanatoimidazole.