AUTHOR=Cai Jian , Wang Xueni , Yang Zaizhun , Tan Yanhui , Peng Bo , Liu Yonghong , Zhou Xuefeng 

TITLE=Thiodiketopiperazines and Alkane Derivatives Produced by the Mangrove Sediment–Derived Fungus Penicillium ludwigii SCSIO 41408

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.857041

DOI=10.3389/fmicb.2022.857041

ISSN=1664-302X

ABSTRACT=<p>A new trithiodiketopiperazine derivative, adametizine C (<bold>1</bold>), and five new alkane derivatives (<bold>7–11</bold>), were isolated from the mangrove sediment–derived fungus <italic>Penicillium ludwigii</italic> SCSIO 41408, together with five known dithiodiketopiperazine derivatives (<bold>2–6</bold>). Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configuration of <bold>1</bold> was determined by X-ray crystallographic analysis. In a variety of bioactivity screening, <bold>1</bold>–<bold>5</bold> exhibited some selective antifungal or antibacterial activities. Compounds <bold>1</bold>–<bold>3</bold> showed cytotoxicity against prostate cancer cell line 22Rv1 with half maximal inhibitory concentration (IC<sub>50</sub>) values of 13.0–13.9 μM; moreover, <bold>3</bold> showed obvious activity against another prostate cancer PC-3 cells with an IC<sub>50</sub> value of 5.1 μM. Further experiments revealed that <bold>3</bold> could significantly reduce PC-3 cells colony formation and induce apoptosis in a dose-dependent manner. Several compounds also exhibited obvious inhibitory activities of lipopolysaccharide–induced nuclear factor-κB with IC<sub>50</sub> values range from 8.2 to 21.5 μM, and <bold>1</bold>, <bold>5</bold>, and <bold>9</bold> were further evaluated for their effects on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. Adametizine C (<bold>1</bold>), with the strongest inhibitory activity against RANKL-induced osteoclast differentiation in bone marrow macrophage cells with 10 μM, was suggested to be the promising lead compound for the treatment of osteoclast-related diseases.</p>