148014-39-5Relevant academic research and scientific papers
Thielavins as glucose-6-phosphatase (G6Pase) inhibitors: Producing strain, fermentation, isolation, structural elucidation and biological activities
Sakemi, Shinichi,Hirai, Hideo,Ichiba, Toshio,Inagaki, Taisuke,Kato, Yoshinao,Kojima, Nakao,Nishida, Hiroyuki,Parker, Janice C.,Saito, Toshiyuki,Tonai-Kachi, Hiroko,VanVolkenburg, Maria A.,Yoshikawa, Nobuji,Kojima, Yasuhiro
, p. 941 - 951 (2002)
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.
Synthesis and biological evaluation of thielocin B1 analogues as protein-protein interaction inhibitors of PAC3 homodimer
Ohsawa, Kosuke,Yoshida, Masahito,Izumikawa, Miho,Takagi, Motoki,Shin-ya, Kazuo,Goshima, Naoki,Hirokawa, Takatsugu,Natsume, Tohru,Doi, Takayuki
supporting information, p. 6023 - 6034 (2018/11/23)
The synthesis and biological evaluation of thielocin B1 analogues have been demonstrated. Fourteen analogues modified in the central core and terminal carboxylic acid moiety were concisely synthesized by simple esterification or etherification reaction. The evaluation of synthetic analogues as inhibitors of proteasome assembling chaperone (PAC) complexes (the PAC3 homodimer and PAC1/PAC2) revealed that the natural product-like bending structure and terminal carboxylic acid groups were crucial for its biological activity. Moreover, SAR and in silico docking studies indicated that all methyl groups on the diphenyl ether moiety of thielocin B1 contribute to the potent and selective inhibition of the PAC3 homodimer via hydrophobic interactions.
Synthesis and phospholipase A2 inhibitory activity of thielocin B3 derivatives.
Teshirogi,Matsutani,Shirahase,Fujii,Yoshida,Tanaka,Ohtani
, p. 5183 - 5191 (2007/10/03)
We prepared several types of derivatives of thielocin B3, a very potent naturally occurring inhibitor for human nonpancreatic secretory PLA2 (sPLA2-II), and conducted a structure-activity relationship study to identify potent sPLA2-II inhibitors with the aim of developing antiinflammatory drugs. The total number of aromatic rings is critical for sPLA2-II inhibition, and the best result was obtained in the case of six rings. The structure of the central part of the inhibitors was not specific, and potent inhibitors were found among the sulfide, sulfone, ether, methylene, and amino derivatives. Although a diester of the terminal carboxylic acid lost its inhibitory activity, having both of the carboxylic acids was not necessary for expression of activity, as illustrated by a glycine derivative with the benzyl ester group 36. Among the newly synthesized derivatives, 18, 20, 29, and 36 showed very potent human sPLA2-II inhibitory activity comparable to that of natural thielocin B3. Their IC50 values are in the range 0.069-0.14 microM, and they are a class of compounds showing the most potent sPLA2-II inhibition to date.
