Synthesis, optical properties, DNA, β-cyclodextrin interaction, hydrogen isotope sensor and computational study of new enantiopure isoxazolidine derivative (ISoXD)
Afnan Alotayeq,
Siwar Ghannay,
Ibrahim A. Alhagri,
Iqrar Ahmed,
Bechir Hammami,
Abuzar E. A. E. Albadri,
Harun Patel,
Sabri Messaoudi,
Adel Kadri,
Sadeq M. Al-Hazmy,
Kaiss Aouadi
Affiliations
Afnan Alotayeq
Department of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia
Siwar Ghannay
Department of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia
Ibrahim A. Alhagri
Department of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia; Department of Chemistry, Faculty of Sciences, Ibb University, Ibb, Yemen
Iqrar Ahmed
Department of Pharmaceutical Chemistry, Prof. Ravindra Nikam College of Pharmacy, Gondur, Dhule, 424002, India; Division of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, 425405, Maharashtra, India
Bechir Hammami
Department of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia
Abuzar E. A. E. Albadri
Department of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia
Harun Patel
Division of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, 425405, Maharashtra, India
Sabri Messaoudi
Department of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia; Faculty of Sciences of Bizerte, Carthage University, Jarzouna, Bizerte 7021, Tunisia
Adel Kadri
Faculty of Science of Sfax, Department of Chemistry, University of Sfax, B.P. 1171, 3000 Sfax, Tunisia; Department of Chemistry, Faculty of Science and Arts of Baljurashi, Al- Baha University, Saudi Arabia
Sadeq M. Al-Hazmy
Department of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia
Kaiss Aouadi
Department of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia; Department of Chemistry, Laboratory of Heterocyclic Chemistry Natural Product and Reactivity/CHPNR, Faculty of Science of Monastir, University of Monastir, Avenue of the Environment, Monastir, 5019, Tunisia; Corresponding author. Department of Chemistry, College of Science, Qassim University, Buraidah, 51452, Saudi Arabia.
A novel isoxazolidine derivative (ISoXD) dye was successfully synthesized and comprehensively characterized. In this study, we conducted a thorough examination of its various properties, including optical characteristics, interactions with DNA and β-cyclodextrin (β-CD), molecular docking, molecular dynamic simulation, and density functional theory (DFT) calculations. Our investigation encompassed a systematic analysis of the absorption and emission spectra of ISoXD in diverse solvents. The observed variations in the spectroscopic data were attributed to the specific solvent's capacity to engage in hydrogen bonding interactions. Remarkably, the most pronounced intensities were observed in glycol, which can establish many hydrogen bonds with ISoXD.Furthermore, our study revealed a significant distinction in the fluorescence behavior of ISoXD when subjected to different solvents, particularly between CHCl3 and CDCl3. Moreover, we explored the fluorescence intensity of the ISoXD complex in the presence of various metals, both in ethanol and water. The ISoXD complex exhibited a substantial increase of fluorescence upon interaction with different metal ions. The utilization of DFT calculations allowed us to propose an intramolecular charge transfer (ICT) mechanism as a plausible explanation for this quenching phenomenon. The interaction of ISoXD with DNA and β-CD was studied using absorption spectra. The binding constant (K) and the standard Gibbs free energy change (ΔGo) for the interaction between DNA and β-CD with ISoXD were determined. In docking study, ISoXD exhibited significant docking scores (−6.511) and MM-GBSA binding free energies (−66.27 kcal/mol) within the PARP-1 binding cavity. Its binding pattern closely resembles to the co-crystal ligand veliparib, and during a 100ns MD simulation, ISoXD displayed strong stability and formed robust hydrogen bonds with key amino acids. These findings suggest ISoXD's potential as a PARP-1 inhibitor for further investigation in therapeutic development.
