br Conflict of interest br Author

Conflict of interest
Author contributions
Introduction 2-Quinolones [quinoline-2(1H)-ones], while less prominent than the isomeric 4-quinolones, nevertheless enjoy significant attention as scaffolds in compounds exhibiting a variety of biological activities. These include: 4-aryl-6-chloroquinolin-2-ones 1 (Fig. 1) prepared by Cheng et al. [1] as in vitro anti-hepatitis B viral agents; 3-indolylquinolin-2(1H)-ones prepared by Kuethe et al. [2] as KDR kinase inhibitors; 3-anilinoquinolin-2(1H)-ones 2 reported by O’Brien et al. [3] as PDK1 enzyme inhibitors; and, more recently,4-hydroxy-2-quinolone-3-carboxamides developed by Mugnaini et al. [4] as cannabinoid receptor 2 (CB2R) ligands. Of particular relevance to our own research on novel HIV-1 enzyme inhibitors are the results reported by Freeman et al. [5] and by Cheng et al. [6] on the synthesis of 2-quinolone derivatives as HIV-1 reverse transcriptase (RT) inhibitors, and a virtual screening approach by Debnath and co-workers [7] to the identification and anti-HIV activity of benzo-fused benzamidazoles and 3-(amidomethyl)-2-quinolones, such as D4476 3, which were specifically designed to bind to the C-terminal domain of the HIV-1 capsid. Thus far only three HIV-1 integrase (IN) inhibitors have been approved for clinical use, viz., Raltegravir (2007) [8], the 4-quinolone derivative, Elvitegravir (2012) [9], and Dolutegravir (2013).[10] Drug resistance issues have arisen with the use of Raltegravir and Elvitegravir [11], and recent studies [12] have indicated that use of Dolutegravir as a monotherapy should be halted. An ongoing search for new lead compounds with HIV-1 IN inhibition potential is clearly warranted and, in Exocytosis paper, we report: (i) the development of a novel synthetic pathway to a series of 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones which contain the privileged 2-quinolone scaffold and which were identified as potential HIV-1 integrase (IN) inhibitors, using in silico modelling methods; [13] and (ii) their biological evaluation as HIV-1 IN inhibitors.
Results and discussion
Conclusions The 2-quinolone moiety is clearly a privileged scaffold for the construction of biologically active compounds and, in this study, Morita-Baylis-Hillman methodology has been successfully used to develop a novel and practicable pathway for the synthesis of series of new 3-aminomethyl- and 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones – the latter compounds specifically designed as potential HIV-1 IN inhibitors. In vitro bioassay confirmed that many of these compounds, in fact, show selective inhibition of the HIV-1 IN enzyme.
Experimental
Acknowledgments