Synthesis, Optical Properties, DNA, β-cyclodextrin Interaction, Hydrogen Isotope Sensor and Computational Study of New Enantiopure Isoxazolidine Derivative (ISoXD)

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Feb 26

PMID 38404822

Authors

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

Soon will be listed here.

Abstract

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 CHCl and CDCl. 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 (ΔG) 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.

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