22048-79-9Relevant academic research and scientific papers
Design, synthesis and structure-activity relationship studies of novel survivin inhibitors with potent anti-proliferative properties
Xiao, Min,Wang, Jin,Lin, Zongtao,Lu, Yan,Li, Zhenmei,White, Stephen W.,Miller, Duane D.,Li, Wei
, (2015/07/15)
The anti-apoptotic protein survivin is highly expressed in most human cancer cells, but has very low expression in normal differentiated cells. Thus survivin is considered as an attractive cancer drug target. Herein we report the design and synthesis of a series of novel survivin inhibitors based on the oxyquinoline scaffold from our recently identified hit compound UC-112. These new analogs were tested against a panel of cancer cell lines including one with multidrug-resistant phenotype. Eight of these new UC-112 analogs showed IC50 values in the nanomole range in anti-proliferative assays. The best three compounds among them along with UC-112 were submitted for NCI-60 cancer cell line screening. The results indicated that structural modification from UC-112 to our best compound 4g has improved activity by four folds (2.2 μM for UC-112 vs. 0.5 μM for 4g, average GI50 values over all cancer cell lines in the NCI-60 panel).Western blot analyses demonstrated the new compounds maintained high selectivity for survivin inhibition over other members in the inhibition of apoptosis protein family. When tested in an A375 human melanoma xenograft model, the most active compound 4g effectively suppressed tumor growth and strongly induced cancer cell apoptosis in tumor tissues. This novel scaffold is promising for the development of selective survivin inhibitors as potential anticancer agents.
Microwave assisted synthesis of a small library of substituted N, N ′-Bis((8-hydroxy-7-quinolinyl)methyl)-1,10-diaza-18-crown-6 ethers
Farruggia, Giovanna,Iotti, Stefano,Lombardo, Marco,Marraccini, Chiara,Petruzziello, Diego,Prodi, Luca,Sgarzi, Massimo,Trombini, Claudio,Zaccheroni, Nelsi
supporting information; experimental part, p. 6275 - 6278 (2010/12/19)
Figure presented. N,N′-Bis-((8-hydroxy-7-quinolinyl)methyl)-1,10- diaza-18-crown-6 ether 1a and its analogue 1c are known as fluorescent sensors of magnesium in living cells. With the aim to investigate the effects of the substitution pattern on the photophysical properties of ligands 1 and their metal complexes, we developed an efficient microwaves enhanced one-pot Mannich reaction to double-armed diaza-crown ligands 1 carrying a variety of substituents. This new protocol is characterized by shorter reaction times, enhanced yields, and improved product purities with respect to the use of conventional conductive heating.
