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.
Highlights
As an important category of nitrogen-containing heterocycles, quinazolines are prevalent in many naturally occurring alkaloids& 2019 The Authors
Such an observation is confirmed by literature studies, which proposed that ultrasonic irradiation may replace a catalyst under definite conditions [47,48]
A straightforward, green and effective protocol for synthesizing new series of bis-quinazolin-4-ones from obtainable precursors under minutes of ultrasonic irradiation was demonstrated on a gram-scale
Summary
As an important category of nitrogen-containing heterocycles, quinazolines are prevalent in many naturally occurring alkaloids. Numerous reports have demonstrated their utilization in several organic conversions [38,39,40] Because of these special advantages, DESs opened novel perspectives to prepare new substances. The impacts of sonication on organic synthesis are imputed to cavitations, which generate extremely high local pressure and temperature inside the formed bubbles When these bubbles collapse, a sufficient amount of energy was generated for performing the chemical reaction and allowing the process to occur with a high yield in a very short time [41,42]. In continuation to our ongoing efforts to develop greener synthetic pathways for organic conversions [43,44,45,46], I wish to report a DES-mediated protocol for greener and atom-economical preparation of novel series of bis-quinazolinones by using commercially available and inexpensive materials under appropriate catalyst-free and ultrasonic conditions
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
