Chlorogenic acid derivatives with alkyl chains of different lengths and orientations: potent alpha-glucosidase inhibitors.
Alpha-glucosidases play important roles in the digestion of carbohydrates and biosynthesis of viral envelope glycoproteins. Inhibitors of alpha-glucosidase are promising candidates for the development of antitype II diabetics and anti-AIDS drugs. Here, we report the synthesis and alpha-glucosidase inhibitory activity of mono- and diketal/acetal derivatives of chlorogenic acid. The diketal derivatives showed more potent inhibitory activity than the monoketals. The 1,7-(5-nonanone) 3,4-(5-nonanone)-chlorogenic acid diketal showed remarkable inhibitory activity against alpha-glucosidases with potency better than that of 1-deoxynojirimycin hydrochloride. Four diasteremers of pelargonaldehyde diacetal and two of monoacetal derivatives of chlorogenic acid were synthesized in this study. They showed significant potent inhibition similar to or more potent than the ketal counterparts. Acetals with the alkyl chain oriented toward position 2 of chlorogenic acid showed more potent activity than those oriented toward position 6.
Ma
Chao-Mei
CM
Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Hattori
Masao
M
Daneshtalab
Mohsen
M
Wang
Lili
L
D000473:Alkanes / Q000737:chemistry*; D000478:Alkylation; D001665:Binding Sites; D002726:Chlorogenic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005750:Gastric Juice / Q000737:chemistry; D001411:Geobacillus stearothermophilus / Q000201:enzymology; D065089:Glycoside Hydrolase Inhibitors; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000473:Alkanes; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D002726:Chlorogenic Acid