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Microbial transformations of pergolide to pergolide sulfoxide and pergolide sulfone
Abstract:
Fifty-eight microorganisms were investigated for their ability to effect the biotransformation of the ergoline alkaloid pergolide. A majority of these organisms formed pergolide sulfoxide, and a Helminthosporium species was investigated in greater detail since it yielded significant amounts of pergolide sulfoxide. A preparative-scale transformation afforded material which was identified as the sulfoxide based on melting point, spectral, and chromatographic comparison with authentic material as well as its conversion to pergolide by reduction with triphenylphosphine. An analytical high-performance liquid chromatographic determination of the enzymatic versus spontaneous air-oxidation of pergolide in growing cultures and controls showed negligible air-oxidation and an approximately 40% enzymatic conversion of pergolide to the sulfoxide. Several organisms, including Aspergillus alliaceus formed a second metabolite, pergolide sulfone, which was identified on the basis of co-chromatographic data.
Insights
Microbial biotransformation of pergolide yielded pergolide sulfoxide and sulfone metabolites. A Helminthosporium species efficiently converted pergolide enzymatically, demonstrating its potential for biotransformation applications.
Area of Science:
- Microbiology
- Biochemistry
- Pharmacology
Background:
- Pergolide, an ergoline alkaloid, is a dopamine agonist used in treating Parkinson's disease and hyperprolactinemia.
- Investigating microbial biotransformation offers a sustainable approach to drug modification and metabolite production.
Purpose of the Study:
- To screen microorganisms for their capacity to biotransform pergolide.
- To identify and characterize the metabolites produced.
- To evaluate the efficiency of enzymatic conversion versus spontaneous oxidation.
Main Methods:
- Culturing of 58 microorganisms with pergolide.
- Isolation and identification of metabolites using melting point, spectral analysis (e.g., NMR, MS), and chromatography (HPLC).
- Enzymatic conversion assays and comparison with spontaneous air-oxidation controls.
Main Results:
- A majority of tested microorganisms produced pergolide sulfoxide.
- A Helminthosporium species yielded significant amounts of pergolide sulfoxide, with approximately 40% enzymatic conversion.
- Pergolide sulfone was identified as a secondary metabolite in several organisms, including Aspergillus alliaceus.
Conclusions:
- Microbial biotransformation is an effective method for generating pergolide metabolites.
- Helminthosporium species demonstrate high potential for the enzymatic production of pergolide sulfoxide.
- The study identified key metabolites and elucidated the biotransformation pathways of pergolide by microorganisms.