Anti-cancer Effects of MW-03, a Novel Indole Compound, by Inducing 15-Hydroxyprostaglandin Dehydrogenase and Cellular Growth Inhibition in the LS174T Human Colon Cancer Cell Line.

Increases in the expression of prostaglandin E2 (PGE2) are widely known to be involved in aberrant growth in the early stage of colon cancer development. We herein demonstrated that the novel indole compound MW-03 reduced PGE2-induced cAMP formation by catalization to an inactive metabolite by inducing 15-hydroxyprostaglandin dehydrogenase through the activation of peroxisome proliferator-activated receptor-γ. MW-03 also inhibited colon cancer cell growth by arresting the cell cycle at the S phase. Although the target of MW-03 for cell cycle inhibition has not yet been identified, these dual anti-cancer effects of MW-03 itself and/or its leading compound(s) on colon cancer cells may reduce colon cancer development and, thus, have potential as a novel treatment for the early stage of this disease.

An imidazoline-aminophenol (IAP) nickel catalyst: structure and catalytic activity in the enantioselective 1,4-addition of 3'-indolyl-3-oxindoles to nitroethylene.

The structure of a nickel complex of imidazoline-aminophenol (IAP) prepared from IAP with Ni(OAc)2 was elucidated as cis-bis(imidazolineaminophenoxide) [Ni(IAP)2]. The [Ni(IAP)2] complex smoothly promoted catalytic asymmetric 1,4-addition of 3'-indolyl-3-oxindole to nitroethylene to provide chiral mixed 3,3'-bisindoles with high enantioselectivities. Mechanistic studies using ESI-MS analyses suggest that one IAP ligand dissociated from [Ni(IAP)2] to generate the Ni-enolate of 3'-indolyl-3-oxindole. From the optically active 3,3'-mixed indole adduct, biologically important 3'-indolyl-3-pyrrolidinoindoline was successfully synthesized in a three-step reaction sequence.

Catalytic asymmetric Friedel-Crafts/protonation of nitroalkenes and N-heteroaromatics.

The catalytic asymmetric Friedel-Crafts/protonation of indoles and pyrroles with α-substituted nitroalkenes to give the corresponding adducts in a highly anti-selective manner was achieved by an imidazoline-aminophenol (L2)-Cu complex. The anti-adducts could be successfully transformed to biochemically important α-substituted ß-heteroarylalkylamines.

Easy access to fully functionalized chiral tetrahydro-ß-carboline alkaloids.

A four-step synthetic route to fully substituted chiral tetrahydro-ß-carbolines (THBCs) is described. Starting from the (R,S,S)-Friedel-Crafts/Henry adduct obtained from three-component coupling of an indole, nitroalkene, and aldehyde catalyzed by imidazoline-aminophenol-CuOTf, the (1S,3S,4R)-THBCs were readily synthesized in a three-step operation including reduction of the nitro-functionality and Pictet-Spengler cyclization.