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点击化学法合成新型金鸡纳啶糖缀合物作为有前景的裂殖体蛋白酶抑制剂。

Click Inspired Synthesis of Novel Cinchonidine Glycoconjugates as Promising Plasmepsin Inhibitors.

机构信息

Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.

出版信息

Sci Rep. 2020 Feb 27;10(1):3586. doi: 10.1038/s41598-020-59477-3.

Abstract

Among all the malaria parasites, P. falciparum is the most predominant species which has developed drug resistance against most of the commercial anti-malarial drugs. Thus, finding a new molecule for the inhibition of enzymes of P. falciparum is the pharmacological challenge in present era. Herein, ten novel molecules have been designed with an amalgamation of cinchonidine, carbohydrate moiety and triazole ring by utilizing copper-catalyzed click reaction of cinchonidine-derived azide and clickable glycosyl alkynes. The molecular docking of developed molecules showed promising results for plasmepsin inhibition in the form of effective binding with target proteins.

摘要

在所有疟原虫中,恶性疟原虫是最主要的物种,它已经对大多数商业抗疟药物产生了耐药性。因此,寻找一种新的分子来抑制恶性疟原虫的酶是当前药理学的挑战。在此,我们利用来源于金鸡纳碱的叠氮化物和可点击糖基炔的铜催化点击反应,设计了十个新型分子,将金鸡纳碱、糖基部分和三唑环融合在一起。所开发的分子的分子对接显示出了在质体朊酶抑制方面的有前景的结果,它们与靶蛋白有效结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d3/7046651/902e5b444e65/41598_2020_59477_Fig1_HTML.jpg

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