Studies on Synthesis and Antitumor Structure-Activity Relationship of Diterpene Lactones of Andrographis panniculata Nees
HAN Guang，DU Gang-jun，XU Qi-tai
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Insititute of Natural Products，Henan University，Kaifeng 475004，China
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Received
Published
2007-11-20
2008-05-10
Issue Date
2008-05-10
Abstract
OBJECTIVE To synthesize diterpene lactones of Andrographis panniculata Nees and study antitumor structure-activity relationship.METHODS 14-deoxy-11,12-didehydroandrographolide,14-deoxyandrographolide,isoandrographolide and andrographolide acid were synthesized from andrographolide.The antitumor activities were observed in leukemia HL-60 cells and in hepatoma H22-implanted mice,the immune functions were tested by delayed type hypersensitivity(DTH) and charcoal particle clearence in mice.RESULTS The structures of the synthesized compounds were confirmed by IR,MS and 1 H-NMR.In vitro,IC50 of compound isoandrographolide and andrographolide was 7.15 and 28.34 μmol·L-1 respectively in HL-60 cells,others were more than 50 μmol·L-1.In vivo,compound andrographolide and isoandrographolide had significent antitumor activities at the dose of 100 mg·kg-1 with 64.4% and 61.2% suppression respectively in subcutaneous H22-implanted mice,others had no effect on tumor growth.At the same dose,the DTH was promoted by compound andrographolide and andrographolide acid and the charcoal particle clearance coefficient was decreased by compound andrographolide,andrographolide acid,14-deoxyandrographolide and 14-deoxy-11,12-didehydroandrographolide,but both were not affected by compound isoandrographolide.CONCLUSION The preliminary pharmacological studies indicated that the lactam ring of the andrographolides is necessary for antitumor activities and the number and site of the double bonds of the five-number lactam ring and 14-OH might be related to antitumor activities.The antitumor activities that with 12,13-double bonds and 14-OH are much stronger.THF ring of isoandrographolide can boost up the antitumor activities possibly.isoandrographolide has better antitumor activities and has no effect on the mice immune function,which suggested that isoandrographolide might be a useful antitumor drug.
HN Gung;DU Gng-jun;XU Qi-ti.
Studies on Synthesis and Antitumor Structure-Activity Relationship of Diterpene Lactones of Andrographis panniculata Nees [J]. Chinese Pharmaceutical Journal, 2008, 43(10): 790-794
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