科研之友
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摘要
Elephantiasis is a classic sign of late-stage lymphatic filariasis. Although the infection can be treated with drugs, the chronic conditions may not be curable by currently available antifilarial drugs. In continuation of our drug discovery program, we identified potent antifilarial activity in a calophyllic acid and isocalophllic acid mixture, which was isolated from the leaves of Calophyllum inophyllum. The mixture inhibited the motility of adult Brugia malayi worms and microfilariae stage parasites at a concentration of 15.6 mu g/mL with an IC50 of 2.1 and 5.5 mu g/mL, respectively, in in vitro studies. The diastereomeric mixture also exhibited moderate in vivo antifilarial activity in the jird (Meriones unguiculatus) model. A few derivatives of calophyllic acid and isocalophyllic acid were prepared and one of the amide derivatives turned out to be the most promising compound against the adult (MIC: 3.9 and IC50: 0.32 mu g/mL) and microfilariae stage (MIC:1.9 and IC50: 0.26 mu g/mL) parasites with a high selectivity index. The amide derivative has superior activity than the parent natural product, as well as the standard antifilarial drug, ivermectin.
- 出版日期2013-6
