Theoretical investigation of structure, anticancer activity and molecular docking of thiourea derivatives

• Published in: Journal of molecular structure 2021-02, Vol.1225, p.129118, Article 129118
• Main Authors: Kirishnamaline, G., Magdaline, J. Daisy, Chithambarathanu, T., Aruldhas, D., Anuf, A. Ronaldo
• Format: Article
• Language: English
• Subjects: ADMET; Antineoplastic; DFT; In silico; Molecular docking; Thiourea
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2020.129118

•Structural and spectral characteristics of three thiourea derivatives were interpreted.•NBO, Mulliken charge, MEP and PES of the compounds were described.•Lower HOMO-LUMO energy gap suggested the high stability of NPT.•The binding ability of the title molecules were explored through molecular docking study.•Anticancer activity and drug likeness of the compounds were assessed through in silico approaches. Quantum chemical computations and in silico biological evaluation of three substituted thiourea derivatives namely (4-nitrophenyl)thiourea (NPT), (3,5-dimethylphenyl) thiourea (DMPT) and 1,3-di-o-tolylthiourea (DTTU) are described in this study. Spectroscopic properties and vibrational analysis of these derivatives have been characterized experimentally through Fourier transform infrared (FT-IR) and Fourier transform Raman (FT-Raman) spectral techniques and theoretically using density functional theory (DFT) method employing B3LYP functional implemented with the 6-311++G(d,p) basis set. Electronic properties such as molecular electrostatic potential (MEP) and HOMO–LUMO analysis were executed to identify the most reactive site and also to identify the charge transfer takes place within the molecules. Besides, the natural bond orbital (NBO) analysis was carried out to explain the delocalization of charge takes place within the molecule due to intramolecular interactions. Molecular docking and molecular dynamics simulation studies verified the inhibitory nature of the title compounds against BRAF (V600E) protein kinase. Assessment of ADMET properties along with the drug-likeness parameter has exposed good drug-like behaviour of the title compounds. Furthermore, through in silico approaches, the thiourea derivatives under study were evaluated for their antineoplastic activity and were shown to possess potential anticancer activity. [Display omitted]