Molecular Modelling, Hirshfeld Surface Analysis, Molecular Docking and Therapeutic Potential of Phenothiazine Derived Quinizarin

Abstract

Phenothiazine derivative synthesized from hydroxy anthraquinone, characterized by X-ray crystallography, spectroscopic, Hirshfeld surface, DFT studies and molecular docking investigation intent to ascertain its anti-cancer activity. The title compound 7-hydroxy-8-Hnaptho[ 2,3-α]phenothiazine-8,13(14H)-dione crystallizes in orthorhombic lattice. UV-VIS, IR, NMR and mass spectrometric data were employed for characterization. Computational chemistry studies are conducted to further detail its geometrical and spectroscopic characteristics performed with unrestricted DFT method at of B3LYP/ 6-311+G (d, p) level and a comparison between the experimental and simulation results was performed. Non-covalent interactions primarily H-bonding and π-π stacking close contacts were observed at intermolecular levels. Small HOMO-LUMO energy gap of 2.2902 eV, shows the stability of molecule and effectiveness towards charge transfer interactions. Furthermore, MEP is used for predicting reactive sites. Based on Hirshfeld surface analysis, there is evidence for a wide range of interactions and a significant contribution from several non-covalent interactions to crystal packing. The bio-viability study was done using pre ADMET tool. The study elaborates the antitumor activity employing in silico molecular docking studies using the protein over-expressed in lymphoma cell lines namely p53 and BCL2 and when compared with standard drug doxorubicin revealed promising results. The study’s results may inspire to develop more potent derivatives and similar scaffolds for cancer treatment and to explore phenothiazine’s role in fields of material science, photochemistry, and catalysis, that can be analyzed from its structural and electronic properties. Hirshfeld surface analysis sheds light on the role of non-covalent interactions in crystal packing, influencing the compound’s solid- state properties.