Synthesis of quinazoline derivatives with new phenolic moieties: in vitro and in silico evaluations as alternative polyphenol oxidase inhibitorsCansu Öztürk, Feyzi Sinan Tokali, Aykut Öztekin, Erbay Kalay, Yalçın Karagöz, and Mine Aksoy Faculty of Science, Department of Chemistry, Atatürk University, Erzurum, Turkey
E-mail: ekalay@kafkas.edu.tr Received: 19 October 2023 Accepted: 15 April 2024 Abstract: Several novel quinazoline derivatives bearing phenolic hydroxyl moiety (2–7) have been produced with good yields and screened for biological activities. All the title compounds were characterized using spectroscopic techniques such as 1H NMR, 13C NMR, FTIR, and HRMS. Then, the anti-browning effects of synthesized quinazoline derivatives were investigated in vitro. The IC50 values for molecules 2–7 were calculated as 0.085, 1.145, 0.106, 6.86, 0.52, 7.07 µM, respectively. Ki constants, which are inhibitory-enzyme binding constants, were calculated by using Lineweaver–Burk graphs as 0.16 ± 0.0620, 0.906 ± 0.3029, 0.055 ± 0.0171, 9.363 ± 2.5809, 0.773 ± 0.3204, 7.863 ± 1.9107 µM, respectively. In computer-aided analysis, to gain insights electrochemical properties, synthesized compounds were analysed theoretically by density functional theory. Molecular docking studies and MD simulations were performed to identify possible inhibitor-enzyme binding interactions. According to obtained results, all the compounds formed hydrogen bonds with Asn 112 and Asn 414, and showed π-cation interaction with Phe2 70, gatekeeper residue in target protein. Supporting the nm level inhibition, MD simulations indicate that protein-inhibitor complex maintain the stability and have high number of hydrogen bond formation during the simulation. Keywords: Quinazoline derivatives; Catechol oxidase; Molecular docking; DFT; MD simulations Full paper is available at www.springerlink.com. DOI: 10.1007/s11696-024-03670-5
Chemical Papers 78 (15) 8321–8332 (2024) |
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