MEFAS, a hybrid of artesunate-mefloquine active against asexual stages of Plasmodium vivax in field isolates, inhibits malaria transmission.
MEFAS, a hybrid of artesunate-mefloquine active against asexual stages of Plasmodium vivax in field isolates, inhibits malaria transmission.
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DOI：
10.1016/j.ijpddr.2021.09.003
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Krettli AU
中科院分区：
文献类型：
--
作者：
Penna-Coutinho J;da Silva Araújo M;Campos Aguiar AC;Sá PM;Rios CT;Medeiros JF;Pereira DB;Boechat N;Krettli AU
人类疟疾仍然是一个公共卫生问题，也是世界上发病率和死亡率的一个重要原因。疟疾控制是通过个人保护和药物治疗来实现的，而恶性疟原虫对大多数抗疟药（包括青蒿素衍生物）的耐药性蔓延阻碍了药物治疗。控制疟疾的关键药理学策略之一是阻止寄生虫传播给它们的蚊子载体。根据这一理论，MEFAS，一种由青蒿琥酯（AS）和甲氟喹合成的杂化盐，在体外对无性恶性疟原虫具有抑制作用，并能显著降低成熟配子体的活力。本文利用间日疟原虫野外分离物进行膜喂养试验，测试了MEFAS对无性间日疟原虫的抑制作用，以及它在达林按蚊中阻断疟疾传播的能力。MEFAS对间日疟原虫的IC50值为6.5 nM。在50 μM时，MEFAS完全阻断了蚊子的卵囊形成，无论对照组的卵囊数量如何。在较低剂量下，MEFAS将卵囊患病率降低了20%以上。在相同剂量下，AS不规律地减少卵囊形成，只对蚊子感染产生轻微抑制。这些结果突出了MEFAS作为一种新的传播阻断分子的潜力，以及它对间日疟原虫和恶性疟原虫的高血分裂活性，代表了进一步开发具有双重抗疟活性的新药的起点。
Human malaria continues to be a public health problem and an important cause of morbidity and mortality in the world. Malaria control is achieved through both individual protection against mosquito bites and drug treatment, which is hampered by the spread of Plasmodium falciparum resistance to most antimalarials, including artemisinin derivatives. One of the key pharmacological strategies for controlling malaria is to block transmission of the parasites to their mosquito vectors. Following this rational, MEFAS, a synthetic hybrid salt derived from artesunate (AS) and mefloquine has been previously reported for its activity against asexual P. falciparum parasites in vitro, in addition to a pronounced reduction in the viability of mature gametocytes. Herein, MEFAS was tested against asexual forms of Plasmodium vivax and for its ability to block malaria transmission in Anopheles darlingi mosquitoes in a membrane feeding assay using P. vivax field isolates. MEFAS demonstrated high potency, with a IC50 of 6.5 nM against asexual forms of P. vivax. At 50 μM, MEFAS completely blocked oocyst formation in mosquitoes, regardless of the oocyst number in the control group. At lower doses, MEFAS reduced oocyst prevalence by greater than 20%. At equivalent doses, AS irregularly reduced oocyst formation and caused only slight inhibition of mosquito infections. These results highlight the potential of MEFAS as a novel transmission-blocking molecule, as well as its high blood schizonticidal activity against P. vivax and P. falciparum field isolates, representing a starting point for further development of a new drug with dual antimalarial activity.
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影响因子：
5.5
作者：
Carter, R
通讯作者：
Carter, R
DOI：
10.4269/ajtmh.13-0708
发表时间：
2014-04
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
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通讯作者：
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影响因子：
11.8
作者：
Lacerda, Marcus V. G.;Fragoso, Silvio C. P.;Bassat, Quique
通讯作者：
Bassat, Quique
影响因子：
9.8
作者：
do Prado, Vania M.;de Queiroz, Thiago B.;Ferreira, Fabio F.
通讯作者：
Ferreira, Fabio F.
DOI：
10.4269/ajtmh.16-0160
发表时间：
2016-12-28
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
Olliaro PL;Barnwell JW;Barry A;Mendis K;Mueller I;Reeder JC;Shanks GD;Snounou G;Wongsrichanalai C
通讯作者：
Wongsrichanalai C