A Novel Derivative of (-)mycousnine Produced by the Endophytic Fungus Mycosphaerella nawae , Exhibits High and Selective Immunosuppressive Activity on T Cells

• Published in: Frontiers in microbiology 2017-07, Vol.8, p.1251-1251
• Main Authors: Wang, Li-Wei, Wang, Jin-Liang, Chen, Jing, Chen, Jia-Jie, Shen, Jia-Wei, Feng, Xiao-Xiao, Kubicek, Christian P, Lin, Fu-Cheng, Zhang, Chu-Long, Chen, Feng-Yang
• Format: Article
• Language: English
• Subjects: (-)mycousnine enamine; dibenzofurane; immunosuppressive activity; Microbiology; Mycosphaerella nawae; T-cell targeting
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2017.01251

An endophytic fungus, ZJLQ129, was isolated from the leaves of the traditional Chinese medicine Smilax china. From the fermentation broth and mycelium, a dibenzofurane compound (-)mycousnine (1) was isolated. Chemical modification of it to the amide derivative (-)mycousnine enamine (2), which is new to science, was found to have high and selective immunosuppressive activity: similar to cyclosporin A, (-)mycousnine enamine (2) selectively inhibited T cell proliferation, suppressed the expression of the surface activation antigens CD25 and CD69 and the formation and expression of the cytokines interleukin-2 as well as interferon γ in activated T cells, but did not show any effect on the proliferation of B cells and cancer cells (PANC-1 and A549) and the activation of macrophages. Furthermore, the cytotoxicity of (-)mycousnine enamine was lower than that of cyclosporin A, and its therapeutic index (TC50/EC50) was 4,463.5, which is five-fold higher than that of cyclosporin A. We conclude that (-)mycousnine enamine (2), the semi-synthestic product prepared from the native product (-)mycousnine (1) of the endophyte M. nawae is a novel effective immunosuppressant showing low toxicity and high selectivity.