Synthesis of andrographolide derivatives: a new family of alpha-glucosidase inhibitors.
Andrographolide (1), the cytotoxic agent of the plant Andrographis paniculata, was subjected to semi-synthetic studies leading to a series of new derivatives, a novel family of glucosidase inhibitors. Nicotination of 3,19-hydroxyls in 15-alkylidene andrographolide derivatives (9) was favorable to alpha-glucosidase inhibition activity. Among them, 15-p-chlorobenzylidene-14-deoxy-11,12-didehydro-3,19-dinicotinateandrographolide (11c) was a very potent inhibitor against alpha-glucosidase with an IC50 value of 6 microM. However, all compounds concerned for beta-glucosidase showed no inhibition. All compounds synthesized were characterized by the analysis of NMR, IR, HRMS spectra and the stereochemistry of 2 was confirmed by X-ray analysis.
Xu
Hai-Wei
HW
New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450052, PR China.
Dai
Gui-Fu
GF
Liu
Gai-Zhi
GZ
Wang
Jun-Feng
JF
Liu
Hong-Min
HM
D035685:Andrographis / Q000737:chemistry; D004224:Diterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D004224:Diterpenes; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; C030419:andrographolide