Synthesis, docking and in vitro evaluation of l-proline derived 1,3-diketones possessing anti-cancer and anti-inflammatory activities

Publication date: 15 April 2020Source: Journal of Molecular Structure, Volume 1206Author(s): V. Porchezhiyan, D. Kalaivani, J. Shobana, S.E. NoorjahanAbstractUnsymmetrical 1,3-diketones with potential anti-cancer as well as anti-inflammatory activities were synthesized via direct coupling reaction between ketones and N-acyl benzotriazoles, based on soft enolisation under mild conditions and characterized by 1H,13C NMR, IR and HRMS. Molecular docking of the synthesized compounds (5a-5j) with the enzymes PTK6 (breast cancer cell), COX-1 and COX-2 (inflammation and pain) revealed 5j to be the potent compound. It was found to inhibit several important mitogen activated protein kinases, preferentially p38β with a binding energy of −11.2 kcal/mol. During in vitro studies for MTT cytotoxicity assay using breast cancer cell line (MDA-MB-231) and HRBC assay for anti-inflammatory studies, the compound 5j exhibited anti-cancer activity with IC50 = 3.4  μM and 94.7% stabilization respectively. Thus the synthesized compounds (5a-5j) with more drug likeliness and high GI values as proved by the Swiss ADME online portal, can be effective in inhibiting breast cancer cells and the associated inflammation.Graphical abstract
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research