Biotransformation of dihydrocapsaicin by human intestinal fungi and the inhibitory effects of metabolites against LSD1
Xin He,
Baojing Zhang,
Peng Cao,
Honglei Wang,
Shan Wu,
Gang Wang,
Fangyu Yang,
Aijing Leng,
Guobiao Liang,
Dawei Li
Affiliations
Xin He
The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; College of Pharmacy, Dalian Medical University, Dalian 116044, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China
Baojing Zhang
College of Pharmacy, Dalian Medical University, Dalian 116044, China
Peng Cao
General Hospital of Northern Theater Command (General Hospital of Shenyang Military Command), Department of Neurosurgery, Shenyang 110016, China
Honglei Wang
The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; College of Pharmacy, Dalian Medical University, Dalian 116044, China
Shan Wu
College of Pharmacy, Dalian Medical University, Dalian 116044, China
Gang Wang
College of Pharmacy, Dalian Medical University, Dalian 116044, China
Fangyu Yang
College of Pharmacy, Dalian Medical University, Dalian 116044, China; General Hospital of Northern Theater Command (General Hospital of Shenyang Military Command), Department of Neurosurgery, Shenyang 110016, China
Aijing Leng
The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
Guobiao Liang
General Hospital of Northern Theater Command (General Hospital of Shenyang Military Command), Department of Neurosurgery, Shenyang 110016, China; Corresponding author.
Dawei Li
The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; Corresponding author.
Dihydrocapsaicin is the main bioactive component in Capsicum plants, which is widely used in China and India as a food drug and additive. In this study, the biotransformation of dihydrocapsaicin was performed using four cultivated human intestinal fungal strains in vitro. Eight metabolites, including seven previously undescribed metabolites (1 and 3−8) and one known analog (2), were obtained. Numerous spectroscopic data, such as NMR and HRESIMS, were collected to determine their structures. Based on the structures of the dihydrocapsaicin metabolites, the main biotransformation reactions were revealed to be hydroxylation, alcohol oxidation, and lactylation. In particular, the lactylation of hydroxyl groups is mainly mediated by Rhizopus oryzae R2701. In addition, metabolite 1 showed significant inhibitory effect on lysine-specific demethylase 1 (LSD1) (IC50 1.99 μM). Therefore, the biotransformation of dihydrocapsaicin by intestinal fungi afforded various derivatives, which were important resources for developing LSD1 inhibitors and potential application in cancer treatment.
