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环状二酮茚满二酮衍生物作为中性粒细胞弹性蛋白酶抑制的未来支架的合成与筛选

Synthesis and screening of cyclic diketone indanedione derivatives as future scaffolds for neutrophil elastase inhibition.

作者信息

S Meena, S Jubie, C Pramila, A Manal T N, S Gigi

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University Al Dawadmi Kingdom of Saudi Arabia

Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research Ooty Tamilnadu India.

出版信息

RSC Adv. 2023 Apr 17;13(17):11838-11852. doi: 10.1039/d3ra00106g. eCollection 2023 Apr 11.

DOI:10.1039/d3ra00106g
PMID:37077993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10107027/
Abstract

Human neutrophil elastase (HNE) and proteinase 3 (Pr3) released from neutrophils at inflammatory sites are the major causes of pathogens in chronic obstructive pulmonary disease (COPD) and various lung tissue derangements, among which cystic fibrosis and blockade of airway passages are chronic. These proteolytic mediatory agents combined with induced oxidative reactions sustain pathogenicity. Cyclic diketone indane-1,3-dione derivatives were designed, and toxicity evaluation predictions were performed . Benzimidazole and hydrazide derivatives of indanedione were synthesized and characterized. Synthesized compounds were run using neutrophil elastase inhibition assay protocols. The compounds exhibit considerable inhibition of neutrophil elastase enzymes.

摘要

在炎症部位从中性粒细胞释放的人中性粒细胞弹性蛋白酶（HNE）和蛋白酶3（Pr3）是慢性阻塞性肺疾病（COPD）中病原体以及各种肺组织紊乱的主要原因，其中囊性纤维化和气道阻塞是慢性的。这些蛋白水解介导剂与诱导的氧化反应共同维持致病性。设计了环状二酮茚满-1,3-二酮衍生物，并进行了毒性评估预测。合成并表征了茚满二酮的苯并咪唑和酰肼衍生物。使用中性粒细胞弹性蛋白酶抑制试验方案对合成的化合物进行测试。这些化合物对中性粒细胞弹性蛋白酶表现出相当大的抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85e6/10107027/ccb3fb773fd6/d3ra00106g-f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85e6/10107027/ccb3fb773fd6/d3ra00106g-f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85e6/10107027/6ba0fdb90854/d3ra00106g-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85e6/10107027/fc58879902ba/d3ra00106g-f6.jpg
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