In Silico Screening of a Novel Inhibitor of β-Ketoacyl Acyl Carrier Protein Synthase I

Bulletin of the Korean chemical society

Ki-Woong Jeong¹  Ju-Un Lee¹  Dong-Il Kang¹  Yangmee Kim¹  Jee-Young Lee¹ 

关键词: FAS;    KAS I;    In silico Screening;    STD-NMR;    Antibiotics;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

β-Ketoacyl acyl carrier protein synthase I (KAS I) is involved in the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and a therapeutic target of designing novel antibiotics. In this study, we performed receptor-oriented pharmacophore-based in silico screening of E. coli KAS I (ecKAS I) with the aim of identifying novel inhibitors. We determined one pharmacophore map and selected 8 compounds as candidates ecKAS I inhibitors. We discovered one antimicrobial compound, YKAe1008, N-(3-pyridinyl) hexanamide, displaying minimal inhibitory concentration (MIC) values in the range of 128-256 μg/mL against MRSA and VREF. YKAe1008 was subsequently assessed for binding to ecKAS I using saturation-transfer difference NMR spectroscopy. Further optimization of this compound will be carried out to improve its antimicrobial activity and membrane permeability against bacterial cell membrane.

【 授权许可】

Unknown