title: Honokiol trimers and dimers via biotransformation catalyzed by Momordica charantia peroxidase: novel and potent α-glucosidase inhibitors.
abstract: Ten honokiol oligomers (1-10), including four novel trimers (1-4) and four novel dimers (5-8), were obtained by means of biotransformation of honokiol catalyzed by Momordica charantia peroxidase (MCP) for the first time. Their structures were established on the basis of spectroscopic methods. The biological results demonstrated that most of the oligomers were capable of inhibiting α-glucosidase with significant abilities, which were one to two orders of magnitude more potent than the substrate, honokiol. In particular, compound 2, the honokiol trimer, displayed the greatest inhibitory activity against α-glucosidase with an IC50 value of 1.38μM. Kinetic and CD studies indicated that 2 inhibited α-glucosidase in a reversible, mixed-type manner and caused conformational changes in the secondary structure of the enzyme protein. These findings suggested that 2 might be exploited as a promising drug candidate for the treatment of diabetes.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: He
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Bo-Yi
authors.initials: BY
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address: cpu_lykong@126.com.
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D055162:Biocatalysis; D001713:Biphenyl Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D017705:Lignans / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015394:Molecular Structure; D029777:Momordica charantia / Q000201:enzymology*; D009195:Peroxidase / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D017705:Lignans; D009195:Peroxidase; D000520:alpha-Glucosidases; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: Biotransformation; CYKVGLSAYRXSSB-UHFFFAOYSA-N; DYOAGEVABPFDNC-UHFFFAOYSA-N; Dimers; FNPFYOKSDVOOEW-UHFFFAOYSA-N; HHIHLTZXYWXIPN-UHFFFAOYSA-N; Honokiol; Momordica charantia peroxidase; Trimers; UDBONMZICYFKDV-UHFFFAOYSA-N; VMMMWRNAKAZJFS-UHFFFAOYSA-N; ZJVLAIHUYUDLQF-UHFFFAOYSA-N; ZVEYNHAIYHXVKI-UHFFFAOYSA-N; α-Glucosidase inhibitor