Sesterterpenes and macrolide derivatives from the endophytic fungus Aplosporella javeedii

Fitoterapia. 2020 Oct:146:104652. doi: 10.1016/j.fitote.2020.104652. Epub 2020 Jun 6.

Abstract

Five sesterterpenes (1-5) including two new compounds (1 and 2), as well as a new (6) and a known macrolide (7) were isolated from the endophytic fungus Aplosporella javeedii. The structures of the new compounds were elucidated by analysis of their 1D and 2D NMR and HRMS data as well as by comparison with the literature. Compound 4 and its acetyl derivatives 4a, 4b, 4c which were prepared by acetylation of 4 exhibited moderate cytotoxicity against the mouse lymphoma cell line L5178Y with IC50 values ranging from 6.2 to 12.8 μM, respectively. Moreover, 4a and 4c exhibited also cytotoxicity against human leukemia (Jurkat J16) and lymphoma (Ramos) cell lines. Compound 7 showed strong cytotoxicity against the L5178Y cell line, as well as against human Jurkat J16 and Ramos cells with IC50 values of 0.4, 5.8, and 4.4 μM, respectively. Mechanistic studies indicated that 7 induces apoptotic cell death. In addition, compounds 3, 4 and 7 showed low antibacterial activities against Mycobacterium tuberculosis H37Rv and compound 6 against Staphylococcus aureus, respectively, with MICs of 100 μM. Preliminary structure-activity relationships are discussed.

Keywords: Antibacterial activity; Aplosporella javeedii; Cytotoxicity; Macrolides; Pro-apoptotic activity; Sesterterpenes.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Ascomycota / chemistry*
  • Brassicaceae / microbiology
  • Cell Line, Tumor
  • China
  • Endophytes / chemistry
  • Humans
  • Macrolides / isolation & purification
  • Macrolides / pharmacology*
  • Mice
  • Molecular Structure
  • Sesterterpenes / isolation & purification
  • Sesterterpenes / pharmacology*
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Macrolides
  • Sesterterpenes

Supplementary concepts

  • Aplosporella javeedii