New arylalkanones from Horsfieldia macrobotrys, effective antidiabetic agents concomitantly inhibiting α-glucosidase and free radicals.
In search of effective antidiabetic agents having therapeutic effect by inhibiting α-glucosidase and preventive effect by scavenging free radicals, Horsfieldia macrobotrys showed promising bioactivity required for the proposed criteria. Bioassay-guided isolation of the stem bark extract resulted in two new arylalkanones named horsfieldone A (1) and maingayone D (2), together with a new flavanone C-glucoside named 8-C-β-d-glucopyranosylpinocembrin (3). Their structures and stereochemistry were determined by spectroscopic techniques as well as Mosher's method. Of isolated compounds, maingayone D (2) was the most potent inhibitors against both α-glucosidases and free radicals. The presence of additional phenolic moieties in 2 clearly indicated their critical roles in inhibitory effects. Further investigation on mechanism underlying α-glucosidase inhibition indicated that maingayone D (2) could retard the enzyme function by both competitive and noncompetitive manners.
Program of Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand; Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Thailand; International Excellent Program, Mulawarman University, Samarinda 75119, East Kalimantan, Indonesia.
Rico
R
Ramadhan
Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Thailand. Electronic address: preecha.p@chula.ac.th.
Preecha
P
Phuwapraisirisan
D000818:Animals; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005609:Free Radicals / Q000037:antagonists & inhibitors* / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007659:Ketones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D026324:Myristicaceae / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
D016166:Free Radical Scavengers; D005609:Free Radicals; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D007659:Ketones; D000520:alpha-Glucosidases
Antioxidant; Arylalkanone; Diabetes; Glucosidase; Horsfieldia macrobotrys; Myristica motley