- N-Heterocyclic Carbenes as a Robust Platform for Surface-Enhanced Raman Spectroscopy
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Surface-enhanced Raman spectroscopy (SERS) underpins a wide range of commercial and fundamental applications. SERS often relies on ligands, usually thiols, bound to a noble metal surface. The difficulty of straightforward thiol synthesis combined with their instability on surfaces highlights the need for alternative ligand design. We present the first example of SERS utilizing N-heterocyclic carbene ligands. A general three step synthesis is presented for functionalized NHC-CO2 adducts. These ligands are deposited on SERS-active gold film-over-nanosphere substrates (AuFONs) in solvent-free and base-free conditions, which prevents fouling. The resulting films are found to be robust and capable of postsynthetic modifications.
- Dejesus, Joseph F.,Trujillo, Michael J.,Camden, Jon P.,Jenkins, David M.
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- Discovery of a Potent FLT3 Inhibitor (LT-850-166) with the Capacity of Overcoming a Variety of FLT3 Mutations
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Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitor resistance that presents a significant clinical challenge. Herein, a series of pyrazole-3-amine derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. The structure-activity relationship and molecular dynamics simulation studies illustrated that the ribose region of FLT3 could be occupied to help address the obstacle of secondary mutations. Among those derivatives, compound 67 exhibited potent and selective inhibitory activities against FLT3-ITD-positive acute myeloid leukemia (AML) cells and possessed equivalent potency against transformed BaF3 cells with a variety of secondary mutations. Besides, cellular mechanism assays demonstrated that 67 strongly inhibited phosphorylation of FLT3 and its downstream signaling factors, as well as induced cell cycle arrest and apoptosis in MV4-11 cells. In the MV4-11 xenograft models, 67 exhibited potent antitumor potency without obvious toxicity. Taken together, these results demonstrated that 67 might be a drug candidate for the treatment of FLT3-ITD-positive AML.
- Cai, Jiongheng,Chen, Yadong,Chen, Yun,Cheng, Jie,Cheng, Zitian,Heng, Hao,Huang, Fei,Jia, Kun,Li, Hongmei,Lu, Shuai,Lu, Tao,Ren, Jiwei,Sheng, Tiancheng,Song, Shiyu,Tang, Weifang,Wang, Zhijie,Wu, Yingli,Zhu, Yifan
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p. 14664 - 14701
(2021/10/12)
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