Kynapcin-12, a New p-Terphenyl Derivative from Polyozellus multiplex, Inhibits Prolyl Endopeptidase.

Abstract

A major histopathological hallmark of Alzheimer's disease (AD) is the presence of amyloid deposits in the parenchyma of the amygdala, hippocampus, and neocortex1}. The principal component of the amyloid is the /3-amyloid protein (A/?), a 39-43 amino acid peptide composedof a portion of the transmembrane domain and the extracellular domain of the amyloid precursor protein (APP)2). The neurotoxicity of the A/3 has been detected in several cell systems, including primary cultured neurons3). The A/3 having an alanine C-terminus is derived from the proteolytic cleavage of the APPby the action of the yet unidentified endoproteolytic enzymes, /3-and y-secretase4). Recent studies have suggested that prolyl endopeptidase could be involved in the processing of the C-terminal portion of the APP in AD5). The prolyl endopeptidase [PEP; EC 3.4.21,26] is a serine protease, which is known to cleave peptide substrates in the C-terminal side of proline residues6). It plays an important role in degradation of the proline-containing neuropeptides such as oxytocin, vasopressin, substance P, neurotensin and angiotensin, which were suggested to participate in learning and memory processes7'8-*. It was found that the PEP

Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential of a cultured Himalayan lichenCetrelia olivetorum

“…Drugs having capacity to scavenge ROS may have the potential to delay its manifestation (Zhao & Zhao, 2013) and may prove immensely effective in treating the condition. Identifying the PEP inhibitors having therapeutic effect against amnesia and dementia highlights the need to analyze novel PEP inhibitors Diderot et al, 2005;Lee & Song, 2000). Based on our literature survey on bioactivities of lichens, it was found that lichens and their metabolites are reported for their medicinal value and therapeutic potential in a number of diseases and health problems, except PEP inhibition.…”

Bioactive Phytochemical Constituents of Wild Edible Mushrooms from Southeast Asia

“…A Korean research group investigated the EtOAc soluble fraction of the mushroom and reported the chemical structure of two active compounds, thelephoric acid (76) and kynapcin-9 (77) with their PEP activities [178]. Another p-terphenyl derivative, named kynapcin-12, having PEP inhibitory activity with an IC 50 value of 1.25 µM, was isolated by Lee and collaborators from a methanolic extract [179]. The correct chemical structure of kynapcin-12 (78) was later assigned by total synthesis [180].…”

Inhibitory effects of polyozellin from Polyozellus multiplex on HMGB1-mediated septic responses

“…The biological activities of isolated compounds had also been investigated. Kynapcin-12, a p-terphenyl derivative, and kynapcin-13 and -28 belonging to benzofuran skeleton, showed propyl endopeptidase inhibitory activities [16,17]. In addition, polyozellin enhanced quinone reductase and glutathione S-transferase activities, which prevent from chemical carcinogenesis in hepa1c1c7 cells [18].…”