期刊
ACS INFECTIOUS DISEASES
卷 7, 期 7, 页码 1945-1955出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.0c00910
关键词
malaria; benzimidazole; pyridobenzimidazole; Plasmodium falciparum; transmission-blocking; gametocytes
资金
- South African Medical Research Council
- NRF Community of Practice Grant [UID: 110666]
- DSI/NRF South African Research Chairs Initiative Grants [UID: 84627, UID: 64763, UID: 64767]
This study identified benzimidazole derivatives with activity against various developmental stages of Plasmodium parasites, showing potential for the development of novel antimalarial drugs.
The continued emergence of resistance to front-line antimalarial treatments is of great concern. Therefore, new compounds that potentially have a novel target in various developmental stages of Plasmodium parasites are needed to treat patients and halt the spread of malaria. Here, several benzimidazole derivatives were screened for activity against the symptom-causing intraerythrocytic asexual blood stages and the transmissible gametocyte stages of P. falciparum. Submicromolar activity was obtained for 54 compounds against asexual blood stage parasites with 6 potent at IC50< 100 nM while not displaying any marked toxicity against mammalian cells. Nanomolar potency was also observed against gametocytes with two compounds active against early stage gametocytes and two compounds active against late-stage gametocytes. The transmission-blocking potential of the latter was confirmed as they could prevent male gamete exflagellation and the lead compound reduced transmission by 72% in an in vivo mosquito feeding model. These compounds therefore have activity against multiple stages of Plasmodium parasites with potential for differential targets.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据