One-Pot Three Component Synthesis of Quinazolin-4(3H)-One Derivatives: Investigation of Photophysical Properties and FRET Application toward Protein Lysozyme

Abstract

A one-pot, three-component reaction between isatoic anhydride, 1,3-diketones, and amines/arylhydrazines catalyzed by a combination of molecular I₂ and Et₃N in open-air affords a series of quinazolin-4(3H)-one derivatives in good yield. The protocol offers an operationally simple, facile, and cost-effective pathway utilizing easily accessible reagents under mild reaction conditions with significant substrate scope. The results of steady state and time-resolved absorption and emission spectroscopy indicate the potential of quinazolin-4(3H)-one derivatives as a fluorescence probe. They exhibit unique photophysical responses in different solvent environments. In addition, they can also act as FRET acceptors during interaction with protein lysozyme. Preliminary biological studies indicate that quinazolin-4(3H)-ones are cell permeable and can be used as a fluorescent probe for bio-imaging of human cervical cancer (HeLa) cells.

Keywords:

• One-pot synthesis
• quinazolin-4(3H)-ones
• I₂/Et₃N as combo-catalyst
• fluorescence
• FRET
• molecular docking
• cell imaging

Author contributions

The manuscript was written through the contributions of all authors. All authors have approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

S.S acknowledges UGC for Dr. D. S. Kothari postdoctoral fellowship. S.M. thanks UGC, New Delhi, India for Senior Research Fellowship (SRF). The authors are grateful to Prof. S. C. Bhattacharya, Department of Chemistry, Jadavpur University and Prof. K. Chattopadhyay, IICB, for providing instrumental facilities during photophysical and imaging studies. We are also thankful to Dr. S. Chall and S. Chowdhury, IICB and Dr. S. S. Maiti, Jadavpur University for their help during biological interpretation and molecular docking. Crystallography was performed at the DST-FIST, India-funded single crystal X-ray diffractometer facility at the Department of Chemistry, University of Calcutta. The financial assistance and instrumental facilities of Centre of Advanced Study (CAS-V, UGC, New Delhi) at Department of Chemistry, University of Calcutta are gratefully acknowledged.