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新型稠合1,2,3-三唑类作为潜在抗冠状病毒药物的合成、生物学评价及分子模拟

Synthesis, biological evaluation and molecular modeling of a novel series of fused 1,2,3-triazoles as potential anti-coronavirus agents.

作者信息

Karypidou Konstantina, Ribone Sergio R, Quevedo Mario A, Persoons Leentje, Pannecouque Christophe, Helsen Christine, Claessens Frank, Dehaen Wim

机构信息

Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium.

Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA, CONICET), Dpto. Farmacia, Fac. Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina.

出版信息

Bioorg Med Chem Lett. 2018 Nov 15;28(21):3472-3476. doi: 10.1016/j.bmcl.2018.09.019. Epub 2018 Sep 22.

DOI:10.1016/j.bmcl.2018.09.019
PMID:30286952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7127349/
Abstract

Synthesis and biological evaluation of a novel library of fused 1,2,3-triazole derivatives are described. The in-house developed multicomponent reaction based on commercially available starting materials was applied and broad biological screening against various viruses was performed, showing promising antiviral properties for compounds 14d, 14n, 14q, 18f and 18i against human coronavirus 229E. Further in silico studies identified the key molecular interactions between those compounds and the 3-chymotrypsin-like protease, which is essential to the intracellular replication of the virus, supporting the hypothesis that the protease is the target molecule of the potential antiviral derivatives.

摘要

描述了一种新型稠合1,2,3 - 三唑衍生物文库的合成及生物学评价。应用了基于市售起始原料的内部开发的多组分反应，并针对多种病毒进行了广泛的生物学筛选，结果表明化合物14d、14n、14q、18f和18i对人冠状病毒229E具有良好的抗病毒特性。进一步的计算机模拟研究确定了这些化合物与3 - 胰凝乳蛋白酶样蛋白酶之间的关键分子相互作用，该蛋白酶对病毒的细胞内复制至关重要，支持了该蛋白酶是潜在抗病毒衍生物的靶分子这一假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/6f10d4d16ed4/fx23_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/7bde6e86368b/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/5bce76207467/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/adeab2b80341/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/bb32c1a0ab6e/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/e73ff673ac78/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/6f10d4d16ed4/fx23_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/7bde6e86368b/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/5bce76207467/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/adeab2b80341/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/bb32c1a0ab6e/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/e73ff673ac78/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39d/7127349/6f10d4d16ed4/fx23_lrg.jpg

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