Antimalarial activity of natural and synthetic prodiginines.
Antimalarial activity of natural and synthetic prodiginines.
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DOI：
10.1021/jm200543y
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发表时间：
2011-08-11
影响因子：
7.3
通讯作者：
Reynolds, Kevin A.
中科院分区：
文献类型：
--
作者：
Papireddy, Kancharla;Smilkstein, Martin;Kelly, Jane Xu;Shweta;Salem, Shaimaa M.;Alhamadsheh, Mamoun;Haynes, Stuart W.;Challis, Gregory L.;Reynolds, Kevin A.
Prodiginines是一类线形和环状吡咯红色色素化合物。本文报道了4种天然的(IC50=1.7-8.0 nM)和3种合成的前列腺素对恶性疟原虫的体外抗疟活性。第一组化合物取代了天然吲哚的末端非烷基吡咯环，活性减弱(IC50和GT；2920 NM)。SET 2和SET 3分别在右侧末端吡咯的3或5位被单取代或双取代。使用烷基或芳基取代基可以观察到很强的体外活性(IC50=0.9-16.0 nM)。在约氏疟原虫感染小鼠中，使用口服给药评估了甲环丙二胺和更有效的合成类似物。每种类似物在每天给药25 mg/kg后，寄生虫血症降低了90%以上，在某些情况下还提供了治愈。最有利的方案是5 mg/kg/d组寄生虫减少率为92%，25 mg/kg/d组寄生虫减少率为100%，无明显体重减轻或临床明显毒性。
Prodiginines are a family of linear and cyclic oligopyrrole red-pigmented compounds. Herein we describe the in vitro antimalarial activity of 4 natural (IC50 = 1.7-8.0 nM) and 3 sets of synthetic prodiginines against Plasmodium falciparum. Set 1 compounds replaced the terminal non-alkylated pyrrole ring of natural prodiginines and had diminished activity (IC50 >2920 nM). Set 2 and set 3 prodiginines were monosubstituted or disubstituted at either the 3 or 5 position of the right hand terminal pyrrole, respectively. Potent in vitro activity (IC50 = 0.9-16.0 nM) was observed using alkyl or aryl substituents. Metacycloprodiginine and more potent synthetic analogs were evaluated in a P. yoelii murine patent infection using oral administration. Each analog reduced parasitemia by more than 90% after 25 mg/kg/day dosing, and in some cases provided a cure. The most favorable profile was 92% parasite reduction at 5 mg/kg/day, and 100% reduction at 25 mg/kg/day without any evident weight loses or clinical overt toxicity.
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DOI：
10.4269/ajtmh.1976.25.26
发表时间：
1976-01-01
影响因子：
3.3
作者：
DAVIDSON, DE;JOHNSEN, DO;KINNAMON, KE
通讯作者：
KINNAMON, KE
DOI：
10.1016/j.jasms.2008.08.002
发表时间：
2008-12-01
影响因子：
3.2
作者：
Chen, Kan;Rannulu, Nalaka S.;Cole, Richard B.
通讯作者：
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影响因子：
2.1
作者：
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NADELSON, J
影响因子：
7.3
作者：
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影响因子：
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作者：
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通讯作者：
RODGERS, GC