2‐Pyridinyl‐4(3H)‐Quinazolinone: A Scaffold for Anti‐influenza A Virus Compounds. (15th June 2015)

• Record Type: Journal Article
• Authors: Liu, Shixu; Wang, Wei; Jiang, Long; Wan, Shengbiao; Zhang, Lijuan; Yu, Rilei; Jiang, Tao
• Is Part Of: Chemical biology & drug design. Volume 86:Number 5(2015:Nov.)
• Page Start: 1221
• Page End: 1225
• Publication Date: 2015-06-15
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12589
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12589-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A series of 2‐pyridinyl‐3‐substituted‐4(3H)‐quinazolinones were synthesized, and their anti‐influenza A virus activities were determined using the cytopathic effect inhibition assay. Most of the compounds were potent with IC₅₀ values ranging from 51.6 to 93.0 <italic>μ</italic><sc>m</sc>, which are better than that of the currently marketed drug ribavirin. The molecular mechanisms of the new compounds were investigated using neuraminidase inhibition assay, cellular NF‐<italic>κ</italic>B signaling pathway inhibition assay, and computational docking. Compound <bold>4e</bold>, which is a N3 imidazol‐1‐ylpropyl‐substituted derivative of 2‐pyridinyl‐4(3H)‐quinazolinone, had the most potent anti‐influenza A virus activity <italic>in vitro</italic>, and inhibited both virus neuraminidase and cellular NF‐<italic>κ</italic>B signaling pathway. In conclusion, 2‐pyridinyl‐4(3H)‐quinazolinone is a new scaffold for the design of potent anti‐influenza A virus compounds, offering an alternative approach to tackle influenza drug resistance.</p> </abstract>