Scopus Publication Detail
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Discoipyrroles A-D: Isolation, structure determination, and synthesis of potent migration inhibitors from Bacillus hunanensis
Youcai Hu; Malia B. Potts; Dominic Colosimo; Mireya L. Herrera-Herrera; Aaron G. Legako; Muhammed Yousufuddin; Michael A. White; John B. MacMillan(Profiled Authors: John B MacMillan; Michael A White)
Journal of the American Chemical Society. 2013;135(36):13387-13392.Abstract
Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase involved in a variety of cellular response pathways, including regulation of cell growth, proliferation, and motility. Using a newly developed platform to identify the signaling pathway/molecular target of natural products, we identified a family of alkaloid natural products, discoipyrroles A-D (1-4), from Bacillus hunanensis that inhibit the DDR2 signaling pathway. The structure of 1-4, determined by detailed two-dimensional (2D) NMR methods and confirmed by X-ray crystallographic analysis has an unusual 3H-benzo[d]pyrrolo][1,3]oxazine-3,5- dione core. Discoipyrroles A-D potently inhibit DDR2 dependent migration of BR5 fibroblasts and show selective cytotoxicity to DDR2 mutant lung cancer cell lines (IC
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