Malononitrile-activated synthesis and anti-cholinesterase activity of styrylquinoxalin-2(1)-ones

• Published in: RSC advances Vol. 1; no. 27; pp. 15966 - 15975
• Main Authors: Mahajan, Sheena, Slathia, Nancy, Nuthakki, Vijay K, Bharate, Sandip B, Kapoor, Kamal K
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 21.04.2020; The Royal Society of Chemistry
• Subjects: Aldehydes; Alzheimer's disease; Aromatic compounds; Chemistry; Cholinesterase; Malononitrile; Synthesis
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d0ra02816a

Herein, we report a base-free malononitrile activated condensation of 3-methylquinoxaline-2(1 H )-one (3MQ) 1 with aryl aldehydes 3a-3ad for synthesis of styrylquinoxalin-2(1 H )-ones (SQs) 4a-4ad with excellent yields. In this reaction, malononitrile activates the aldehyde via Knoevenagel condensation towards reaction with 3MQ 1 and gets liberated during the course of reaction to yield the desired SQs 4a-4ad . The SQs were evaluated for in vitro cholinesterase inhibition and 4n was found to display a mixed type of inhibition of AChE, which was supported by molecular modelling studies. This study has led to the discovery of a new chemotype for cholinesterase inhibition which might be useful in finding a remedy for Alzheimer's disease. SQs displaying anti-Alzheimer activity is serendipitous. Malononitrile as a handle to facilitate nucleophilic attack has been applied for the first time for the easy access of SQs.