Two new aromatic tenvermectins from mutant Streptomyces avermitilis HU02-06

Area of Science:

• Natural Product Chemistry
• Microbiology
• Pharmacology

Background:

• Streptomyces avermitilis is a known producer of avermectins, a class of potent anthelmintic and insecticidal compounds.
• The exploration of microbial secondary metabolites continues to yield novel bioactive molecules.
• Aromatic tenvermectins (TVMs) represent a less-explored subclass with potential for unique biological activities.

Purpose of the Study:

• To isolate and characterize new aromatic tenvermectins from Streptomyces avermitilis.
• To evaluate the biological activities of the newly discovered compounds, specifically nematocidal and cytotoxic effects.

Main Methods:

• Fermentation of Streptomyces avermitilis HU02-06.
• Isolation and purification of compounds using chromatographic techniques.
• Structure elucidation using comprehensive spectroscopic methods (1D/2D NMR, HRESIMS).
• Bioassays for nematocidal activity against Bursaphelenchus xylophilus and cytotoxic activity against HepG2 and HCT116 cell lines.

Main Results:

• Two new aromatic tenvermectins, 13-oleandrosyl-oleandrosyloxy ST906 (1) and aromatic TVM B (2), were successfully isolated.
• The structures of compounds 1 and 2 were confirmed through detailed spectroscopic analysis.
• Compound 1 and 2 demonstrated weak nematocidal activity against Bursaphelenchus xylophilus.
• Compounds 1 and 2 exhibited moderate cytotoxic activity against HepG2 and HCT116 tumor cell lines.

Conclusions:

• The study successfully identified and characterized two novel aromatic tenvermectins from Streptomyces avermitilis.
• The new TVMs possess preliminary biological activities, including weak nematocidal and moderate cytotoxic effects, suggesting potential for further development.
• This discovery expands the known chemical diversity of tenvermectins and highlights their potential as leads for new therapeutic agents.