Antimalarial activity of piperidine alkaloids from Senna spectabilis and semisynthetic derivatives
Antimalarial activity of piperidine alkaloids from Senna spectabilis and semisynthetic derivatives
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DOI：
10.5935/0103-5053.20140195
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发表时间：
2014-10-01
影响因子：
1.4
通讯作者：
Bolzani, Vanderlan S.
中科院分区：
文献类型：
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作者：
Pivatto, Marcos;Baccini, Luciene R.;Bolzani, Vanderlan S.
在我们继续从巴西生物群中寻找新的抗感染先导化合物的过程中，从番泻花中分离出了两个已知的哌啶生物碱(-)-卡辛和(-)-spectaline。狭叶决明(Cassia Spectabilis)。通过光谱分析和光谱数据分析相结合的方法确定了它们的结构。进一步，这些化合物被乙酰化，得到衍生物(-)-3-O-乙酰卡西林和(-)-3-O-乙酰五味子碱。所有化合物都在培养中筛选出抗恶性疟原虫感染的红细胞(RBC)，目的是鉴定抗疟疾原型。在所筛选的化合物中，前两个生物碱的IC50分别为1.82和2.76 mU M，高于氯喹的标准化合物(IC50分别为24.47和25.14 mU M)(IC50为0.30 mM)。这些数据表明，哌啶生物碱是一类具有广泛生物活性的天然产物，因此是药物设计的重要模板，包括抗疟疾药物。
In our continuing work looking for new anti-infective lead compounds from Brazilian biomes, the two known piperidine alkaloids (-)-cassine and (-)-spectaline were isolated from the flowers of Senna spectabilis (syn. Cassia spectabilis). Their structures were elucidated using a combination of spectroscopic and spectrometric data analysis. Further, these compounds were acetylated yielding the derivatives (-)-3-O-acetylcassine and (-)-3-O-acetylspectaline. All compounds were screened against P. falciparum-infected red blood cells (RBC) in culture, aiming to identify antimalarial prototypes. Among all compounds screened, the first two alkaloids (IC50 1.82 mu M and IC50 2.76 mu M) were more effective than the derivatives (IC50 24.47 mu M and IC50 25.14 mu M) in comparison to the standard compound chloroquine (IC50 0.30 mu M). These data show that piperidine alkaloids constitute a class of natural products that feature a broad spectrum of biological activities, and are, therefore, important templates for drug design, including antimalarial.