کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1394934 | 1501094 | 2016 | 13 صفحه PDF | دانلود رایگان |
• Amide derivatives of augustic, 2-epi-corosolic and asiatic acid were synthesized.
• They were tested for their antitumor activity using human cancer cell lines.
• An augustic acid derived 4-isoquinolinyl amide showed increased cytotoxicity.
• A 4-isoquinolinyl derivative of asiatic acid (28) gave EC50 = 80 nM (A2780 cells).
• The compounds act by apoptosis.
2,3-Di-O-acetyl-triterpenoic acid derived amides possessing a (2β, 3β) configuration in ring A and two acetyl groups were previously shown to possess high cytotoxicity for human tumor cell lines but to exhibit low cytotoxicity for non-malignant mouse fibroblasts. In this study, augustic acid (1) and 2-epi-corosolic acid (2) were chosen as starting points for the synthesis of analogs. While augustic acid derived 3-quinolinyl amide 9 gave low EC50 values in SRB assays but was cytotoxic for all lines, the isomeric 4-isoquinolinyl amide 21 was very cytotoxic for the tumor cell lines but significantly less cytotoxic for the mouse fibroblasts NIH 3T3. In addition, a triacetylated 4-isoquinolinyl derivative of asiatic acid (28) gave EC50 = 80 nM (for A2780 ovarian cancer cells). As shown by additional experiments (acridine orange/propidium iodide staining, fluorescence spectroscopy and cell cycle investigations) these compounds act mainly by apoptosis.
A small structural difference (3-quinolinyl/4-isoquinolinyl) has a strong impact on cytotoxicity and malignant/non-malignant cell selectivity.Figure optionsDownload as PowerPoint slide
Journal: European Journal of Medicinal Chemistry - Volume 122, 21 October 2016, Pages 452–464