Deep eutectic solvent for an expeditious sono-synthesis of novel series of bis-quinazolin-4-one derivatives as potential anti-cancer agents

Abstract

To produce a new category of anti-cancer compounds, a facile and environmentally sustainable method for preparing diversified bis-quinazolinones was demonstrated using recyclable deep eutectic solvent (DES) under ultrasonic irradiation. The reactions were performed smoothly with a wide scope of substrates affording the desired derivatives in good-to-excellent yields under an atom-economical pathway. Particularly, halogen substituents that are amenable for further synthetic elaborations are well tolerated. Furthermore, the ‘greenness’ of the protocol was assessed within the scope of several green metrics and found to display an excellent score in the specified parameters. Cytotoxic activity of all novel bis-quinazolinones was investigated utilizing two cancer cell lines: breast (MCF-7) and lung (A549) cell lines and their IC50 values were determined. Most of the prepared derivatives displayed fascinating inhibitory activity with IC50 values in a low micromolar range. Remarkably, the derivative 7e [3,3'-(sulfonylbis(4,1-phenylene))bis(2-methyl-6-nitroquinazolin-4(3H)-one)] showed superior potency against MCF-7 and A549 cancer cell lines, with IC50 values of 1.26 µM and 2.75 µM, respectively. Moreover, this derivative was found to have low toxicity to the normal breast cell line (MCF-10A) and could serve as a promising lead candidate for further development.

Keywords

• sono-synthesis
• bis-quinazolin-4-ones
• anti-cancer agents
• deep eutectic solvent