In vitro anti-malarial interaction and gametocytocidal activity of cryptolepine.
In vitro anti-malarial interaction and gametocytocidal activity of cryptolepine.
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DOI：
10.1186/s12936-017-2142-z
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发表时间：
2017-12-28
期刊：
影响因子：
3
通讯作者：
Wright CW
中科院分区：
文献类型：
--
作者：
Forkuo AD;Ansah C;Mensah KB;Annan K;Gyan B;Theron A;Mancama D;Wright CW
发现新型杀配子细胞分子是消除和根除疟疾的主要药理学策略。在加纳的传统和医院环境中，西非流行的抗疟疾植物 Cryptolepis sanguinolenta（Periplocaceae）的水根提取物的大量使用，促使本研究调查该植物及其主要生物碱 Cryptolepine 的配子细胞杀灭活性。随着寻找新的抗疟疾组合的继续，这项研究还调查了隐磷脂与标准抗疟疾药物的抗疟疾相互作用。基于刃天青的测定用于评估 C. sanguinolenta 和 Cryptolepine 对恶性疟原虫 (NF54) 晚期 (IV/V) 配子细胞的杀配子细胞特性。采用基于 SYBR Green I 荧光测定的固定比率方法，使用氯喹敏感菌株 3D7，在体外构建隐磷脂与四种标准抗疟疾药物组合的等效线图。 Cryptolepis sanguinolenta (IC50 = 49.65 nM) 及其主要生物碱 Cryptolepine (IC50 = 1965 nM) 对恶性疟原虫 (NF54) 的晚期配子体表现出高抑制活性。在无性阶段的相互作用测定中，隐芴平与本芴醇和氯喹均表现出相加效应，平均 ΣFIC50 分别为 1.017 ± 0.06 和 1.465 ± 0.17。隐松平与阿莫地喹以治疗相关浓度比组合显示出协同作用（平均ΣFIC50 = 0.287 ± 0.10），而甲氟喹则出现拮抗活性（平均ΣFIC50 = 4.182 ± 0.99）。这项研究的结果揭示了 C. sanguinolenta 和 Cryptolepine 的高配子细胞杀伤特性，将其有效的抗疟疾活性主要归因于它们对寄生虫有性和无性阶段的影响。阿莫地喹是 Cryptolepine 在开发新型固定剂量组合中的潜在药物伙伴。
Discovery of novel gametocytocidal molecules is a major pharmacological strategy in the elimination and eradication of malaria. The high patronage of the aqueous root extract of the popular West African anti-malarial plant Cryptolepis sanguinolenta (Periplocaceae) in traditional and hospital settings in Ghana has directed this study investigating the gametocytocidal activity of the plant and its major alkaloid, cryptolepine. This study also investigates the anti-malarial interaction of cryptolepine with standard anti-malarials, as the search for new anti-malarial combinations continues. The resazurin-based assay was employed in evaluating the gametocytocidal properties of C. sanguinolenta and cryptolepine against the late stage (IV/V) gametocytes of Plasmodium falciparum (NF54). A fixed ratio method based on the SYBR Green I fluorescence-based assay was used to build isobolograms from a combination of cryptolepine with four standard anti-malarial drugs in vitro using the chloroquine sensitive strain 3D7. Cryptolepis sanguinolenta (IC50 = 49.65 nM) and its major alkaloid, cryptolepine (IC50 = 1965 nM), showed high inhibitory activity against the late stage gametocytes of P. falciparum (NF54). In the interaction assays in asexual stage, cryptolepine showed an additive effect with both lumefantrine and chloroquine with mean ΣFIC50s of 1.017 ± 0.06 and 1.465 ± 0.17, respectively. Cryptolepine combination with amodiaquine at therapeutically relevant concentration ratios showed a synergistic effect (mean ΣFIC50 = 0.287 ± 0.10) whereas an antagonistic activity (mean ΣFIC50 = 4.182 ± 0.99) was seen with mefloquine. The findings of this study shed light on the high gametocytocidal properties of C. sanguinolenta and cryptolepine attributing their potent anti-malarial activity mainly to their effect on both the sexual and asexual stages of the parasite. Amodiaquine is a potential drug partner for cryptolepine in the development of novel fixed dose combinations.
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影响因子：
3
作者：
Stepniewska, Kasia;Price, Ric N.;Sutherland, Colin J.;Drakeley, Chris J.;von Seidlein, Lorenz;Nosten, Francois;White, Nicholas J.
通讯作者：
White, Nicholas J.
影响因子：
15.8
作者：
Delves M;Plouffe D;Scheurer C;Meister S;Wittlin S;Winzeler EA;Sinden RE;Leroy D
通讯作者：
Leroy D
影响因子：
3.7
作者：
Amoah LE;Kakaney C;Kwansa-Bentum B;Kusi KA
通讯作者：
Kusi KA
影响因子：
5.2
作者：
Pradines, B;Tall, A;Doury, JC
通讯作者：
Doury, JC
影响因子：
--
作者：
Zhang, JH;Chung, TDY;Oldenburg, KR
通讯作者：
Oldenburg, KR