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New Avermectin Analogues from a Mutant Streptomyces avermectinius Strain
Youjun Zhang1,2, Cheng Zhang1, Keke Wang1
1Research Center for Marine Drugs, School of Pharmacy, Second Military Medical University, 325 Guo-He Road, Shanghai, 200433, P. R. China.
Chemistry & Biodiversity
|April 8, 2017
Summary
Researchers discovered two novel avemectin analogues from a Streptomyces avermectinius mutant strain. These compounds show moderate cytotoxic activity against B16, MG-63, and Saos-2 cancer cell lines in laboratory tests.
Area of Science:
- Microbiology
- Natural Product Chemistry
- Pharmacology
Background:
- Streptomyces avermectinius is a key producer of avermectins, important antiparasitic agents.
- Genetic manipulation of Streptomyces strains can lead to novel compound discovery.
- The 'b' series of avermectins are less explored compared to other series.
Purpose of the Study:
- To isolate and characterize new avemectin analogues from a genetically modified Streptomyces avermectinius strain.
- To investigate the cytotoxic potential of the isolated novel compounds.
Main Methods:
- Fermentation of a ∆aveCDE mutant Streptomyces avermectinius strain.
- Isolation and purification of compounds using chromatographic techniques.
- Structure elucidation via Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS).
- In vitro cytotoxicity assays against B16, MG-63, and Saos-2 cell lines.
Main Results:
- Two new avemectin analogues, designated 1 and 2, belonging to the 'b' series were successfully isolated.
- The chemical structures of compounds 1 and 2 were determined through comprehensive spectroscopic analysis.
- Both compounds exhibited moderate cytotoxic effects on the tested cancer cell lines.
Conclusions:
- The genetic modification of Streptomyces avermectinius facilitated the production of novel avemectin analogues.
- Avemectin analogues 1 and 2 possess cytotoxic properties, suggesting potential for further investigation in cancer research.
- This study expands the known diversity of avermectin compounds and their biological activities.