Effect of o-difluoro and p-methyl substituents on the structure, optical properties and anti-inflammatory activity of phenoxy thiazole acetamide derivatives: Theoretical and experimental studies

• Published in: Journal of molecular structure 2020-01, Vol.1199, p.127024, Article 127024
• Main Authors: Khamees, Hussien Ahmed, Mohammed, Yasser Hussein Eissa, S, Ananda, Al-Ostoot, Fares Hezam, Y, Sangappa, Alghamdi, Saad, Khanum, Shaukath Ara, Madegowda, Mahendra
• Format: Article
• Language: English
• Subjects: DFT studies; Energy framework; In silico docking; In vitro COX; Molecular dynamics; Structural analysis
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2019.127024

Thiazole derivatives (6a and 6b) have been synthesized and characterised by 1H –13C NMR, as well as LC-MS spectra. The three-dimensional structures have been confirmed by single crystal X-ray diffraction method. 6a and 6b compounds have been crystallized in the Triclinic and the Orthorhombic systems with P-1 and Pbca space groups, respectively. Supramolecular structures revealed the stability of molecules with different intermolecular interactions and different crystal packing environment. Theoretical study by Density functional theory (DFT) with B3LYP functional based on highest basis set 6–311++G(d,p) was employed to calculate the geometry and compared to the experimental data. The electronic structures and intramolecular charge transfers have been investigated by using natural population and natural bond orbital analysis (NBO). Further, DFT studies were performed to assess the frontier molecular orbitals (FMOs), energy gap, softness, hardness, and others chemical reactivity. Hirshfeld surface was investigated to distinguish the different interatomic contacts and understand the crystal packing of molecules with aid of energy frameworks through different intermolecular interaction energies based on the anisotropy of the topology. Nonlinear optical property (NLO) of the synthesized molecules were predicted by (DFT) and examined experimentally by using second harmonic generation (SHG) and revealed the importance of high NLO based on the nature of substituents and conformation. Thiazole derivatives were assessed for anti-inflammation activity by in silico molecular docking studies against COX-1 and COX-2 protein receptors revealed prominent interactions with active site and further molecular dynamics confirms the stability of the protein-ligand model. In vitro assay against cyclooxygenase (COX) enzyme gave IC50 values of 6a and 6b molecules with ortho-difluoro and para-methyl positions on benzoyl group, showed better inhibitor for COX-1 and COX-2, respectively. [Display omitted] •The structure of thiazole compounds are confirmed by single crystal XRD and investigated by Hirshfeld surface analyses.•NPA and NBO analysis revealed the nature of hydrogen bonds and intramolecular charge transfer based on the substituents.•NLO activity was confirmed by SHG and β values were discussed with effect of different substituents and conformation.•Docking and Molecular dynamics simulations performed to predict the COX enzyme inhibitor.•In vitro anti-inflammatory activity ag