In vitro interaction of artemisinin derivatives or the fully synthetic peroxidic anti-malarial OZ277 with thapsigargin in Plasmodium falciparum strains.
In vitro interaction of artemisinin derivatives or the fully synthetic peroxidic anti-malarial OZ277 with thapsigargin in Plasmodium falciparum strains.
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DOI：
10.1186/1475-2875-12-43
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发表时间：
2013-01-31
期刊：
影响因子：
3
通讯作者：
Wittlin S
中科院分区：
文献类型：
--
作者：
Abiodun OO;Brun R;Wittlin S
半合成青蒿素衍生物是青蒿素类复方疗法中的强效过氧化物药物，被推荐作为疾病流行国家恶性疟原虫疟疾的一线治疗药物。Eckstein-Ludwig及其同事的研究表明，毒胡萝卜素和青蒿素都能特异性抑制恶性疟原虫的肌浆网Ca 2 +− ATP酶（PfATP 6）。在本研究中，在寄生虫培养物中评估毒胡萝卜素和青蒿素衍生物以及臭氧化物OZ 277（RBx 11160或arterolane）之间的相互作用类型。后一种化合物是一种金刚烷基过氧化物，是Ranbaxy实验室有限公司最近在印度注册的第一种用于抗疟疾联合治疗的全合成临床候选药物。使用先前描述的固定比例方法进行药物相互作用研究，并使用[3 H]次黄嘌呤掺入试验测量抗疟疾活性。毒胡萝卜素与OZ 277、蒿甲醚或青蒿琥酯相互作用对恶性疟原虫NF 54和K1株的50%和90%分数抑制浓度（∑ FIC 50，90）的总和为0.9至1.4。毒胡萝卜素与OZ 277、青蒿琥酯或蒿甲醚的相互作用是相加的，数据与先前的观察结果一致，表明抗疟疾过氧化物的活性并不来自与寄生虫靶标的可逆相互作用。
Semi-synthetic artemisinin derivatives are powerful peroxidic drugs in artemisinin-based combination therapy (ACT) recommended as first-line treatment of Plasmodium falciparum malaria in disease-endemic countries. Studies by Eckstein-Ludwig and co-workers showed both thapsigargin and artemisinin specifically inhibit the sarcoplasmic reticulum Ca2+−ATPase of Plasmodium falciparum (PfATP6). In the present study the type of interaction between thapsigargin and artemisinin derivatives as well as the ozonide OZ277 (RBx11160 or arterolane) was evaluated in parasite cultures. The latter compound is an adamantane-based peroxide and the first fully synthetic clinical candidate recently registered in India by Ranbaxy Laboratories Ltd. for anti-malarial combination therapy. Drug interaction studies were performed using a previously described fixed ratio method and anti-malarial activity measured using the [3H] hypoxanthine incorporation assay. The sum 50% and 90% fractional inhibitory concentration (∑FIC50, 90) of the interaction of thapsigargin with OZ277, artemether or artesunate, against NF54 and K1 strains of P. falciparum ranged from 0.9 to 1.4. The interaction of thapsigargin with OZ277, artesunate or artemether was additive, data consistent with previous observations indicating that activity of anti-malarial peroxides does not derive from reversible interactions with parasite targets.
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影响因子：
4.8
作者：
Bhisutthibhan, J;Pan, XQ;Meshnick, SR
通讯作者：
Meshnick, SR
影响因子：
64.8
作者：
Eckstein-Ludwig, U;Webb, RJ;Krishna, S
通讯作者：
Krishna, S
影响因子：
2.1
作者：
CANFIELD, CJ;PUDNEY, M;GUTTERIDGE, WE
通讯作者：
GUTTERIDGE, WE
DOI：
10.1039/9781849733496-00033
发表时间：
2011-01-01
期刊：
NEGLECTED DISEASES AND DRUG DISCOVERY
影响因子：
--
作者：
Tilley, Leann;Charman, Susan A.;Vennerstrom, Jonathan L.
通讯作者：
Vennerstrom, Jonathan L.
影响因子：
64.8
作者：
Vennerstrom, JL;Arbe-Barnes, S;Charman, WN
通讯作者：
Charman, WN