Synthesis, Crystal Structure and Biological Evaluation of Novel 2-Phenylthiazole Derivatives as Butyrylcholinesterase Inhibitors

• Published in: Journal of chemical research Vol. 42; no. 7; pp. 366 - 370
• Main Authors: Shi, Da-Hua, Ma, Xiao-Dong, Liu, Yu-Wei, Min, Wei, Yin, Fu-Jun, Tang, Zong-Ming, Song, Meng-Qiu, Lu, Chen, Song, Xiao-Kai, Liu, Wei-Wei, Dong, Tong
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.07.2018; Sage; Sage Publications Ltd
• Subjects: Chemistry; Chemistry, Multidisciplinary; Crystal lattices; Crystal structure; Derivatives; Docking; Inhibitors; NMR; Nuclear magnetic resonance; Physical Sciences; Science & Technology; Single crystals; Surface analysis (chemical); Two dimensional analysis; X-ray diffraction; 2-phenylthiazole derivatives; cholinesterase; Alzheimer's disease; crystal structure formation; DESIGN; ACETYLCHOLINESTERASE; MOLECULAR DOCKING
• ISSN: 1747-5198; 2047-6507
• DOI: 10.3184/174751918X15314837408346

To find novel butyrylcholinesterase inhibitors, three novel 2-phenylthiazole derivatives were synthesised. The synthesised compounds were characterised by NMR and single-crystal X-ray diffraction analysis. Hirshfeld surface analysis and two-dimensional fingerprint plots of the compounds were used as a theoretical approach to assess the driving force for crystal structure formation via the intermolecular interactions in the crystal lattices of the synthesised compounds. Among the three compounds, N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl)-2-(4-methoxyphenyl)thiazole-4-carboxamide showed the best butyrylcholinesterase-inhibition activity with an IC50 value of 75.12 μM. A docking study demonstrated that this compound interacts with the peripheral anionic site of butyrylcholinesterase.