Synthesis, vibrational spectroscopic investigations, molecular docking, antibacterial studies and molecular dynamics study of 5-[(4-nitrophenyl)acetamido]-2-(4-tert-butylphenyl)benzoxazole

• Published in: Journal of molecular structure 2017-04, Vol.1133, p.557-573
• Main Authors: Sheena Mary, Y., Al-Shehri, Mona M., Jalaja, K., Al-Omary, Fatmah A.M., El-Emam, Ali A., Yohannan Panicker, C., Armaković, Stevan, Armaković, Sanja J., Temiz-Arpaci, Ozlem, Van Alsenoy, C.
• Format: Article
• Language: English
• Subjects: ALIE; BDE; Benzoxazole; DFT; Docking; RDF
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2016.12.020

Antimicrobial active 5-[(4-nitrophenyl)acetamido]-2-(4-tert-butylphenyl)benzoxazole (NATPB) was synthesized and observed IR, Raman bands are compared with the theoretically predicted wave numbers. In the IR spectrum the NH stretching wave number splits into a doublet with a noted difference and is red shifted from the computed value, which indicates the weakening of NH bond resulting in proton transfer to the neighbouring oxygen atom. The HOMO-LUMO plots reveal the charge transfer in the molecular system through the conjugated paths. The electrophilic and nucleophilic reactive sites are identified from the MEP plot. Mapping of average local ionization energy (ALIE) values to the electron density surface served us as a tool for prediction of molecule sites possibly prone to electrophilic attacks. Other important reactive centres of the title molecule were detected by calculations of Fukui functions. Calculations of bond dissociation energies (BDE) for hydrogen abstraction were used in order to assess whether the NATPB molecules is prone to autoxidation mechanism or not, while BDE of the remaining single acyclic bonds were used in order to determine the weakest bond. Interaction properties with water were investigated by molecular dynamics (MD) simulations and calculations of radial distribution functions (RDFs). The compound possessed broad spectrum activity against all of the tested Gram-positive and Gram-negative bacteria and yeasts, their minimum inhibitory concentrations (MICs) ranging between 32 and 128 μg/ml. The compound exhibited significant antibacterial activity (32 μg/ml) against an antibiotic resistant E. faecalis isolate, at same potency with the compared standard drugs vancomycin and gentamycin sulfate. The molecular docking studies show that the compound might exhibit inhibitory activity against CDK inhibitors. [Display omitted] •IR and Raman spectra were measured.•Exhibits significant antibacterial activity.•ALI, BDE, RDF have been discussed in detail.•Exhibits inhibitory activity against CDK inhibitors.