Theoretical and experimental investigation of novel quinazoline derivatives: synthesis, photophysical, reactive properties, molecular docking and selective HSA biointeraction

Abstract

Two new quinazoline derivatives (2a and 2b) were successfully synthesized in this work using the condensation technique in excellent yields. Using spectroscopic techniques and elemental analyses, the compounds were completely characterized. Density functional theory (DFT) computations have been used to examine the title compound’s reactive characteristics. Chemical reactivity was predicted using local reactive descriptors and molecule electrostatic potential. Additionally, Time dependent DFT (TD-DFT) simulations were used to examine the impact of solvents on the photophysical characteristics. The affinity of compounds 2a and 2b for human serum albumin (HSA) was further explored using several electronic spectroscopies. Through static mechanisms, both compounds reduce the intrinsic fluorescence of HSA. It is determined that the HSA-2b complex’s binding constant is significantly greater than the HSA-2a complex. The fluorescence spectrum measurements proved that the HSA underwent structural changes after interaction with these compounds. It was demonstrated by site marker competitive displacement studies that compounds 2a and 2b preferred to bind to site I in HSA subdomain IIA. Additionally, synchronised fluorescence spectra were utilized to analyze how HSA’s conformation changed after interacting with various substances. The molecular docking investigations of these compounds with the three critical HSA binding sites, comprising subdomains IIA, IIIA, and IB, further confirmed the experimental findings. The significant contact between the investigated compounds and HSA was supported by the docking simulations.

Communicated by Ramaswamy H. Sarma

Keywords:

• Quinazoline
• photophysical
• DFT
• HSA
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the authors.

Acknowledgments

The authors immensely express their indebted gratitude to the Management of BNM Institute of Technology for providing lab facilities to carry out this work. The authors extend their thanks and appreciation to Research Supporting Project (Ref: RSP2023R160) King Saud University, Riyadh, Saudi Arabia. Byong-Hun Jeon thanks Korea Institute of Energy Technology Evaluation and Planning (KETEP) grants funded by the Ministry of Trade, Industry and Energy (MOTIE) of the South Korean Govt. (No.20206410100040) for funding. Byong-Hun Jeon thank Hanyang University, Seoul, Republic of Korea.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.