Thielavins as glucose-6-phosphatase (G6Pase) inhibitors: Producing strain, fermentation, isolation, structural elucidation and biological activities

Article abstract of DOI:10.7164/antibiotics.55.941

High-throughput screening of microbial extracts using rat hepatic microsomal glucose-6-phosphatase (G6Pase) led us to find thielavin B as a G6Pase inhibitor with inhibition of glucose output from glucagon-stimulated hepatocytes. Further searching for more potent analogs identified 11 new thielavins F～P in addition to the known thielavins A and B from a fungus Chaetomium carinthiacum ATCC 46463. Thielavin G showed the strongest activity as a G6Pase inhibitor (IC₅₀=0.33 μM), while the IC₅₀ of thielavin B was 5.5 μM. According to the structure-activity relationship, including authentic thielavins C, D and 3 partial hydrolysates from thielavins A and B, 3 benzoic acid-units and carboxylic acid functions are essential for G6Pase inhibition.