Issue 34, 2019

NHC-catalyzed green synthesis of functionalized chromones: DFT mechanistic insights and in vitro activities in cancer cells

Abstract

An efficient synthesis of 3-aminochromones and 3-alkylchromones by a N-heterocyclic carbene (NHC) catalyzed intramolecular hydroacylation reaction of corresponding salicylaldehyde derived nitriles and activated alkynes respectively in ionic liquids under microwave conditions is reported. This protocol has the advantages of environmental friendliness, higher yields, shorter reaction times, and convenient operation using the commercially available thiazolium catalyst. The origin of the chemical reactivity of the NHC-catalyzed intramolecular hydroacylation reaction of nitriles is studied using Density Functional Theory (DFT). The results suggest that 3-aminochromone formation occurs via an acyl anion intermediate called a Breslow intermediate (INT2) through TS2. The Breslow intermediate (INT2) forms a carbon–carbon bond with the nitrile carbon to produce an imine intermediate INT3viaTS3, which further undergoes imine to amine tautomerism to give the end product. Some of the derivatives of 3-aminochromone are subjected to amine functionalization in one pot to obtain a library of compounds for anticancer activity. Among the investigated compounds, 2c (SVM-2), 4c (SVM-4) and 2d (SVM-9) show IC50 values of 5.18, 4.89 and 27.3 μM respectively in HeLa S3 cancer cells. Compound 5c (SVM-5) shows IC50 values of 13.3 and 14.2 μM in A549 and HeLa S3 cancer cells, respectively. Compounds 2c (SVM-2) and 4c (SVM-4) produce morphological changes and control the colony formation in HeLa S3 cells, which indicates that these small molecules are potential candidates for anticancer drugs.

Graphical abstract: NHC-catalyzed green synthesis of functionalized chromones: DFT mechanistic insights and in vitro activities in cancer cells

Supplementary files

Article information

Article type
Paper
Submitted
22 May 2019
Accepted
20 Jul 2019
First published
23 Jul 2019

New J. Chem., 2019,43, 13509-13525

NHC-catalyzed green synthesis of functionalized chromones: DFT mechanistic insights and in vitro activities in cancer cells

N. Murugesh, J. Haribabu, K. Arumugam, C. Balachandran, R. Swaathy, S. Aoki, A. Sreekanth, R. Karvembu and S. Vedachalam, New J. Chem., 2019, 43, 13509 DOI: 10.1039/C9NJ02650A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements