Anti-Aβ42 Aggregative Polyketides from the Antarctic Psychrophilic Fungus Pseudogymnoascus sp. OUCMDZ-3578

Abstract

Seven new polyketides, diphenyl ketone (1), diphenyl ketone glycosides (2−4), diphenyl ketone-diphenyl ether dimer (6), and anthraquinone-diphenyl ketone dimers (7 and 8), together with compound 5, were isolated from the psychrophilic fungus Pseudogymnoascus sp. OUCMDZ-3578 fermented at 16 °C and identified by spectroscopic analysis. The absolute configurations of 2−4 were determined by acid hydrolysis and 1-phenyl-3-methyl-5-pyrazolone precolumn derivatization. The configuration of 5 was first determined by X-ray diffraction analysis. Compounds 6 and 8 showed the highest activity against amyloid beta (Aβ 42 ) aggregation with half-maximal inhibitory concentrations (IC 50 ) of 0.10 and 0.18 μM, respectively. They also showed strong abilities to chelate with metal ions, especially iron, were sensitive to Aβ 42 aggregation induced by metal ions, and displayed depolymerizing activity. Compounds 6 and 8 show potential as leads for the treatment of Alzheimer's disease to prevent Aβ 42 aggregation.

Isatin-based spiro indolenine alkaloids from Isatis indigotica Fortune with anti-neuroinflammatory and acetylcholinesterase inhibitory effects

“…Alzheimer's disease (AD) is a major public health problem, affecting more than 20 million people worldwide. [20][21][22][23] The increased oxidative stress and decreased acetylcholine (ACh) were believed to be critical factors in the development of AD. [24][25][26][27] To establish the appropriate experimental concentration of the four compounds, a CCK-8 kit was adopted to detect the BV2 cell viability.…”

Expanding the Toolbox for Genetic Manipulation in Pseudogymnoascus: RNAi-Mediated Silencing and CRISPR/Cas9-Mediated Disruption of a Polyketide Synthase Gene Involved in Red Pigment Production in P. verrucosus

“…Fungi from the genus Pseudogymnoascus exhibit interesting capabilities in their specialized metabolism [15][16][17][18][19][20][21]. To gain a deeper understanding of Pseudogymnoascus' metabolic potential, molecular tools enabling its genetic manipulation are essential.…”

“…From a biotechnological perspective, numerous studies have demonstrated that extracts derived from diverse strains of Pseudogymnoascus harbor bioactive metabolites with antibacterial, antifungal, trypanocidal, herbicidal, and antitumoral properties [9][10][11][12][13][14]. Furthermore, chemical analyses of Pseudogymnoascus strains have revealed that members of this fungal genus produce different classes of compounds, such as sesquiterpenes [15], macrolides [16], polyketides [17,18], tetrapeptides [19], and various nitrogenous compounds [20,21]. This underscores the potential of Pseudogymnoascus as a prolific source of specialized metabolites.…”