Antiparasitic activity of alkaloids from plant species of Papua New Guinea and Australia
Antiparasitic activity of alkaloids from plant species of Papua New Guinea and Australia
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DOI：
10.1016/j.ijantimicag.2010.05.008
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发表时间：
2010-09-01
影响因子：
10.8
通讯作者：
Avery, Vicky M.
中科院分区：
文献类型：
--
作者：
Fernandez, Liza S.;Sykes, Melissa L.;Avery, Vicky M.
需要新药来帮助克服引起疟疾和锥虫病等疾病的寄生虫中日益严重的抗药性问题。本研究从巴布亚新几内亚的福林德西亚(Flindersia Bobinensis)、竹节莲(Stephania Zippeliana)、罂粟(Voacanga Papuana)和澳大利亚的弗林德西亚(Flindersia Acumata)植物提取物中分离得到生物碱化合物，研究其对恶性疟原虫株和布氏锥虫的抗寄生活性以及对哺乳动物细胞系HEK 293和HeLa的细胞毒作用。其中活性最强的化合物二甲基异丁香碱(DMIB)对恶性疟原虫敏感株和耐药株具有亚微摩尔活性，半数抑制浓度(IC(50))在20 nm~810 nm之间，对恶性疟原虫具有中等的选择性。布鲁斯和哺乳动物细胞。阶段特异性研究表明，恶性疟原虫滋养体阶段的寄生虫比环状或裂殖体阶段的寄生虫对DMIB更敏感。DMIB处理后的滋养体表现出食物空泡形态的变化，血球蛋白的形成明显减少，这似乎不是通过与血红素的直接结合来抑制的。这些发现表明，从Flindersia spp.中提取吲哚生物碱是可能的。作为新的抗寄生虫剂。(C)2010年Elsevier B.V.和国际化疗学会。版权所有。
New drugs are needed to help overcome the increasing problem of drug resistance in parasites that cause diseases such as malaria and trypanosomiasis. In this study, alkaloid compounds isolated from extracts of the plants Flindersia amboinensis, Stephania zippeliana and Voacanga papuana from Papua New Guinea and Flindersia acuminata from Australia were examined for their antiparasitic activity against Plasmodium falciparum strains and Trypanosoma brucei brucei as well as their cytotoxicity against the mammalian cell lines HEK 293 and HeLa. The most active compound, dimethylisoborreverine (DMIB), showed sub-micromolar activity, with 50% inhibitory concentration (IC(50)) values between 20nM and 810nM both against drug-sensitive and drug-resistant P. falciparum strains, along with moderate selectivity against T.b. brucei and mammalian cells. Stage specificity studies revealed that P. falciparum trophozoite-stage parasites were more susceptible to DMIB than ring- or schizont-stage parasites. DMIB-treated tropho-zoites showed changes in food vacuole morphology, with an apparent reduction in haemozoin formation that does not appear to be inhibited via the direct binding of haem. These findings suggest a potential for indole alkaloids from Flindersia spp. as new antiparasitic agents. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.