کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1368980 | 981737 | 2015 | 5 صفحه PDF | دانلود رایگان |
Gambogic acid (GA), a natural product with unique structure, was reported to have broad antiproliferation activities against cancer cell lines. As a reactive Michael acceptor, the 10-position of GA is susceptible to nucleophiles, thus limiting its clinical application as an anticancer agent. Moreover, the 6-OH forms an intramolecular hydrogen bond with 8-CO, which can make the 9, 10 double bond more reactive to nucleophiles. In this essay, two strategies (A and B) were applied to solve the above-mentioned problems. Strategy A was to increase the steric hindrance of C-10 to reduce the activity of GA towards nucleophiles. Strategy B was to replace the hydroxyl of C-6 with other substituents based on the assumption that the intra-molecular hydrogen bond could increase the electrophilicity of C-10. Results showed the electrophilicity of C-10 disappeared as well as the antiproliferation activity against cancer cell lines by introducing a methyl group at C-10. Strategy B showed that the electrophilicity of C-10 was reduced dramatically while maintained the activity by replacement of the hydroxyl of C-6 with neutral or basic groups.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 25, Issue 14, 15 July 2015, Pages 2844–2848