N-Substituted Bridged Azaozonides as Promising Antimalarial Agents.

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2025-04-17 DOI:10.1002/cmdc.202500181

Paolo Coghi, Ivan A Yaremenko, Parichat Prommana, Ali Adnan Nasim, Yulia Yu Belyakova, Ruihong Chen, Peter S Radulov, Chairat Uthaipibull, Alexander O Terent'ev, Vincent Kam Wai Wong

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Abstract

Forty-five aminoperoxides belonging to bridged azaozonides, bridged N-substituted azaozonides, and tricyclic aminoperoxides were evaluated for in vitro antimalarial activity against Plasmodium falciparum (3D7) and for cytotoxicity against immortalized human normal liver (LO₂) and lung (BEAS-2B) cell lines, as well as human liver (HepG2) and lung (A549) cancer cell lines. Seven N-substituted azaozonides exhibited high antimalarial activity against the chloroquine-sensitive 3D7 strain of P. falciparum, with IC₅₀ < 1 μM. The lead compound 22 showed IC₅₀ = 0.07 μM and selectivity index of 1428. Most aminoperoxides were generally non-cytotoxic to both normal and cancer liver and lung cells. Only two azaozonides exhibited moderate cytotoxicity on HepG2 cell line (2: IC₅₀ = 4.12 μM, 40: 9.95 μM), while one azaozonide 2 had an IC₅₀ = 5.56 μM against A549 cell line. From this small library of 45 aminoperoxides, compound 22 was found to have antimalarial activity comparable to artemisinin and chloroquine used in medical practice. These findings provide a new source for developing antimalarial agents through structural modification of aminoperoxide compounds.

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n取代桥接偶氮杂脲作为抗疟药的前景。

研究了桥接氮杂脲类、桥接n -取代氮杂脲类和三环胺过氧化物等45种氨基过氧化物对恶性疟原虫（3D7）的体外抗疟活性、对永生化人正常肝（LO2）和肺（BEAS-2B）细胞系以及人肝（HepG2）和肺（A549）癌细胞的细胞毒性。7种氮代氮杂虫对氯喹敏感的恶性疟原虫3D7株具有较高的抗疟活性，IC50 = 0.07 μM，选择性指数为1428。大多数氨基过氧化物对正常和癌变的肝、肺细胞一般都没有细胞毒性。两种偶氮腙对HepG2细胞株的IC50分别为4.12 μM和9.95 μM，其中一种偶氮腙对A549细胞株的IC50分别为5.56 μM。从这个由45种氨基过氧化物组成的小文库中，发现化合物22具有与医疗实践中使用的青蒿素和氯喹相当的抗疟疾活性。这些发现为通过氨基过氧化物化合物的结构修饰开发抗疟药物提供了新的来源。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.