The microbial biotransformation of P-synephrine and isolation of its metabolites by using analytical methods with their antidiabetic and antimicrobial activities

A number of factors such as nutrition, physiological and disease status, antibiotic use and hygiene conditions play a role in the development of microbiota. As a result of the observations of epidemiological and metagenomic studies and with the data obtained from different experimental animal models, it has been shown that the development of common diseases such as allergic diseases, colorectal cancer, diabetes, obesity is associated with the change of intestinal microbiota. Treatment with probiotics such as Lactobacillus or Bifidobacterium species lasting 4-12 weeks has shown significant improvements in body fat mass and insulin sensitivity in individuals. It is possible to obtain chemical derivatives with physicochemical properties such as high stereospecificity and regioselectivity with environmentally friendly microbial biotransformation reactions. p-Synephrine, which is an alkaloid found in Citrus aurantium var. Amara, can show effective properties with bacteria in biotransorption and is generally used in dietary supplements. When we look at the studies on the biotransformation of alkaloids, there is not much scientific data. In a study conducted in China in 2016, 4,5-dimethoxy-canthen-6-one alkaloid type compound was biotransformed by Cunninghamella blakesleeana CGMCC 3,970 mushroom and a total of 6 compounds were obtained, 1 of which was new. In this thesis, in vitro microbial biotransformation of p-synephrine was performed for the first time using Lactobacillus acidophilus ATCC 4356 bacterial strain. The butanol and aqueous phase extracts obtained and they were subjected to separation processes by chromatographic analysis. Then, the structures of the pure compounds obtained were clarified using spectroscopic methods such as 1H-NMR, APT and MS. Thus, tyramine and octopamine substances were obtained based on synephrine. Antidiabetic activities of the compounds were investigated and the IC50 value of the tyramine (SLS-39-1) was found to be 484,909 µg/mL, the IC50 value of the octopamine (SLM-21-30-1) was found to be > 500 µg/mL and the IC50 value of SLS-1-22 (tyramine, synephrine) fraction was found to be 109,7 µg/mL. The α-glucosidase inhibition activities of biotransformed compounds were investigated. Tyramine (SLS-39-1) showed the highest antimicrobial activity. With this thesis, besides the biotransformation of the synephrine, new biological activities can be brought to the molecules, the formation of new compounds, the production of new metabolites based on a single substance (with the support of methods such as HPLC and OrbiTRAP L/MS) and the anti-diabetic properties of these metabolites. Activities were enabled to be evaluated.