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首页> 外文期刊>Combinatorial Chemistry _High Throughput Screening >A New Library of C-16 Modified Artemisinin Analogs and Evaluation of Their Anti-Parasitic Activities
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A New Library of C-16 Modified Artemisinin Analogs and Evaluation of Their Anti-Parasitic Activities

机译:C-16修饰的青蒿素类似物的新库及其抗寄生虫活性的评价

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A library of C-16 modified artemisinin analogs was prepared and their antimalarial as well as antileishmanial activities were evaluated. Synthesis of these compounds involved the conversion of artemisinin to its phenol derivatives 7 and 12, and subsequent parallel derivatization by introducing new chemical groups through ester, carbamate, sulfate, phosphate and isourea linkages. Comparison of in vitro antimalarial activities showed that C9-α artemisinin analogs (8a-f) are more potent than the corresponding C9-β diastereomers (9a-f); however, their antileishmanial activities were in the same range. Many of the 10-deoxoartemisinin analogs studied here showed promising antiparasitic activities. For example, compounds 13a-e are approximately three times more active against drug resistant W2 strain of P. falciparum, compared to artemisinin (IC50, ∼0.2 - 0.6 nM; cf. artemisinin = 1.6 nM). Further, a number of compounds in this series were notably leishmanicidal, with activities comparable to or better than pentamidine (e.g., 13g and 13j). Detailed in vivo studies involving these active compounds are underway to identify lead candidates for further development.
机译:制备了C-16修饰的青蒿素类似物文库,并评估了其抗疟和抗疟疾活性。这些化合物的合成涉及将青蒿素转化为其酚衍生物7和12,然后通过酯,氨基甲酸酯,硫酸根,磷酸根和异脲键引入新的化学基团,随后进行平行衍生。体外抗疟活性的比较表明,C9-α青蒿素类似物(8a-f)比相应的C9-β非对映异构体(9a-f)更有效。但是,他们的屠夫活动在同一范围内。此处研究的许多10-脱氧青蒿素类似物均显示出有希望的抗寄生虫活性。例如,与青蒿素相比,化合物13a-e的抗恶性疟原虫W2菌株的活性约为青蒿素的三倍(IC50,约0.2-0.6 nM;参见青蒿素= 1.6 nM)。此外,该系列中的许多化合物具有明显的杀菌作用,其活性与喷他tam相当或更好(例如13g和13j)。正在进行涉及这些活性化合物的详细体内研究,以鉴定可进一步开发的潜在候选药物。

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