New secondary metabolites with immunosuppressive activity from the phytopathogenic fungus Bipolaris maydis

• Published in: Bioorganic chemistry Vol. 99; pp. 103816 - 103820
• Main Authors: Duan, Xueyan, Tan, Xiaosheng, Gu, Lianghu, Liu, Junjun, Hao, Xincai, Tao, Li, Feng, Hao, Cao, Yunfang, Shi, Zhengyi, Duan, Yulin, Deng, Mengyi, Chen, Gang, Qi, Changxing, Zhang, Yonghui
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.06.2020; Elsevier
• Subjects: Animals; Biochemistry & Molecular Biology; Bipolaris - chemistry; Bipolaris - metabolism; Bipolaris maydis; Cell Proliferation - drug effects; Chemistry; Chemistry, Organic; Dose-Response Relationship, Drug; Immunosuppressive; Immunosuppressive Agents - chemistry; Immunosuppressive Agents - metabolism; Immunosuppressive Agents - pharmacology; Life Sciences & Biomedicine; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Male; Meroterpenoid; Mice; Mice, Inbred C57BL; Molecular Structure; Murine splenocytes; Orchidaceae - chemistry; Orchidaceae - metabolism; Physical Sciences; Plant Leaves - chemistry; Plant Leaves - metabolism; Science & Technology; Sesterterpene; Sesterterpenes - chemistry; Sesterterpenes - metabolism; Sesterterpenes - pharmacology; Spleen - drug effects; Structure-Activity Relationship; Immunosuppressive; Meroterpenoid; Murine splenocytes; Sesterterpene; Bipolaris maydis; MEROTERPENOIDS
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.103816

[Display omitted] •Three new compounds (1–3) were isolated from Bipolaris maydis.•2 and 3 could inhibit anti-CD3/anti-CD28 mAbs activated murine splenocyte proliferation.•2 and 3 could inhibit lipopolysaccharide activated murine splenocyte proliferation.•First report of ophiobolin-type sesterterpenoids as immunosuppressor. Three previously undescribed compounds, including a meroterpenoid, guignardone T (1), and two ophiobolin-type sesterterpenoids, maydispenoids A and B (2 and 3), along with four known compounds (4–7), were isolated from the phytopathogenic fungus Bipolaris maydis collected from Anoectochilus roxburghii (Wall.) Lindl leaves. The structures of all undescribed compounds were elucidated by spectroscopic analysis, electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction. Structurally, maydispenoids A was characterized by a fascinating decahydro-3-oxacycloocta[cd]pentalene fragment. It is notable that the compounds 2 and 3 exhibited potential inhibitory activity in anti-CD3/anti-CD28 monoclonal antibodies (mAbs) stimulated murine splenocytes proliferation, with IC50 values of 5.28 and 9.38 μM, respectively, and also suppress the murine splenocytes proliferation activated by lipopolysaccharide (LPS), with IC50 values of 7.25 and 16.82 μM, respectively. This is the first report of ophiobolin-type sesterterpenoids as immunosuppressor, and may provide new chemical templates for the development of new immunosuppressive drugs for autoimmune disease treatment.