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海洋来源真菌中的丁烯内酯类化合物的抗炎、抗过敏和 COVID-19 主要蛋白酶(M)抑制活性。

Anti-Inflammatory, Antiallergic, and COVID-19 Main Protease (M) Inhibitory Activities of Butenolides from a Marine-Derived Fungus .

机构信息

Department of Pharmacognosy, Faculty of Pharmacy, Ankara University, Ankara 06560, Turkey.

Department of Pharmacognosy, Faculty of Pharmacy, Agri Ibrahim Cecen University, Agri 04100, Turkey.

出版信息

Molecules. 2021 Jun 2;26(11):3354. doi: 10.3390/molecules26113354.

Abstract

In December 2020, the U.K. authorities reported to the World Health Organization (WHO) that a new COVID-19 variant, considered to be a variant under investigation from December 2020 (VUI-202012/01), was identified through viral genomic sequencing. Although several other mutants were previously reported, VUI-202012/01 proved to be about 70% more transmissible. Hence, the usefulness and effectiveness of the newly U.S. Food and Drug Administration (FDA)-approved COVID-19 vaccines against these new variants are doubtfully questioned. As a result of these unexpected mutants from COVID-19 and due to lack of time, much research interest is directed toward assessing secondary metabolites as potential candidates for developing lead pharmaceuticals. In this study, a marine-derived fungus was investigated, affording two butenolide derivatives, butyrolactones I () and III (), a meroterpenoid, terretonin (), and 4-hydroxy-3-(3-methylbut-2-enyl)benzaldehyde (). Chemical structures were unambiguously determined based on mass spectrometry and extensive 1D/2D NMR analyses experiments. Compounds (-) were assessed for their in vitro anti-inflammatory, antiallergic, and in silico COVID-19 main protease (M) and elastase inhibitory activities. Among the tested compounds, only revealed significant activities comparable to or even more potent than respective standard drugs, which makes butyrolactone I () a potential lead entity for developing a new remedy to treat and/or control the currently devastating and deadly effects of COVID-19 pandemic and elastase-related inflammatory complications.

摘要

2020 年 12 月,英国当局向世界卫生组织(WHO)报告称,通过病毒基因组测序发现了一种新的 COVID-19 变体,被认为是 2020 年 12 月(VUI-202012/01)开始调查的变体。尽管之前已经报道了其他几种突变体,但 VUI-202012/01 被证明具有约 70%更高的传染性。因此,新获得美国食品和药物管理局(FDA)批准的 COVID-19 疫苗对这些新变体的有效性和效果令人怀疑。由于 COVID-19 出现了这些出人意料的突变体,而且时间紧迫,因此人们将大量研究兴趣集中在评估次生代谢产物作为开发先导药物的潜在候选物上。在这项研究中,研究了一种海洋来源的真菌,得到了两个丁烯内酯衍生物,丁内酯 I () 和 III (), 一个倍半萜烯,terretonin () 和 4-羟基-3-(3-甲基-2-丁烯基)苯甲醛 ()。基于质谱和广泛的 1D/2D NMR 分析实验,明确确定了化合物的化学结构。对化合物 (-) 进行了体外抗炎、抗过敏和 COVID-19 主要蛋白酶(M)和弹性蛋白酶抑制活性的评估。在所测试的化合物中,只有 显示出与相应标准药物相当或甚至更有效的显著活性,这使得丁内酯 I () 成为开发新疗法以治疗和/或控制 COVID-19 大流行和弹性蛋白酶相关炎症并发症目前破坏性和致命性影响的潜在先导实体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dcd/8199578/222c6e8a3a24/molecules-26-03354-g001.jpg

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