Kangning Wei, Kaige Guo, Ye Tao, Xuanming Gong, Guobing Yan, Liangliang Wang, Ming Guo
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Design, synthesis, biological evaluation and molecular docking of novel isatin-oxime ether derivatives as potential IDH1 inhibitors.
A series of novel isatin-oxime ether derivatives were designed, synthesized and characterized by 1H NMR and 13C NMR and HRMS. These compounds were evaluated for their in vitro cytotoxicity against three human cancer cell lines (A549, HepG2 and Hela) by MTT assay. According to the experimental results, compounds 6a (IC50 = 0.34μM), 6c (IC50 = 14nM) and 6r (IC50 = 45nM) were found as the excellent selectivity and high activity against A549, whereas compounds 6m (IC50 = 12nM) and 6n (IC50 = 25nM) displayed the significant activity for HepG2, respectively. Compound 6f (IC50 = 30nM), 6n (IC50 = 9nM) and 6o (IC50 = 20nM) also showed the excellent activity against Hela. From the experiments of cell migration and colony formation assays, the findings demonstrated that 6m can effectively suppress the migration and growth of HepG2 cells. In addition, the results of molecular docking studies determined the strong binding interactions between the potential active compounds 6m and 6n and the active sites of isocitrate dehydrogenase 1 (IDH1) with the lowest binding affinity energy.
期刊介绍：
Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including:
combinatorial chemistry and parallel synthesis;
small molecule libraries;
microwave synthesis;
flow synthesis;
fluorous synthesis;
diversity oriented synthesis (DOS);
nanoreactors;
click chemistry;
multiplex technologies;
fragment- and ligand-based design;
structure/function/SAR;
computational chemistry and molecular design;
chemoinformatics;
screening techniques and screening interfaces;
analytical and purification methods;
robotics, automation and miniaturization;
targeted libraries;
display libraries;
peptides and peptoids;
proteins;
oligonucleotides;
carbohydrates;
natural diversity;
new methods of library formulation and deconvolution;
directed evolution, origin of life and recombination;
search techniques, landscapes, random chemistry and more;
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