Biotransformation of (-)-cubebin by Aspergillus spp. into (-)-hinokinin and (-)-parabenzlactone, and their evaluation against oral pathogenic bacteria

Abstract

The biotransformation of the lignan (-)-cubebin by filamentous fungi Aspergillus terreus and Aspergillus niger is an efficient bioprocess for obtaining (-)-hinokinin and (-)-parabenzlactone. The relevance of getting (-)-hinokinin is due to its promising effect against oral pathogens, especially S. sanguinis (both MIC and MBC 12.5 μg/mL), and other previous reported effects against Chagas disease and as anti-inflammatory. The advantage of using fungal transformation is the use of non-toxic and/or non-pollutant reagents and/or solvents in comparison with semi-synthesis. Microbial transformation of (-)-cubebin is also important to evaluate its human metabolism, since Aspergillus species are capable of mimicking P450 reactions, providing possible products of the metabolism, which is important in the assessment of its efficacy and safety. Furthermore, the present study describes a reliable RP-HPLC method to perform quantification of (-)-hinokinin in fungal extracts. It is simple, fast, selective, linear, precise, accurate and robust according to validation guidelines.

Keywords:

• (-)-Hinokinin
• (-)-cubebin
• Aspergillus spp
• biotransformation
• oral bacteria
• (-)-parabenzlactone
• analytical method

Acknowledgements

Authors are thankful to São Paulo Research Foundation (FAPESP), CNPq and CAPES for both financial support and scholarships.