306315-47-9Relevant academic research and scientific papers
Identification of novel vacuolin-1 analogues as autophagy inhibitors by virtual drug screening and chemical synthesis
Chen, Chang,Lu, Yingying,Siu, Ho Ming,Guan, Jintao,Zhu, Longchao,Zhang, Shuang,Yue, Jianbo,Zhang, Liangren
, (2017/06/19)
Autophagy is a fundamental cellular degradation process which is essential for cell homeostasis, and dysfunctional autophagy has been associated with a variety of human diseases, such as cancer. Several autophagy chemical modulators have been applied in a number of preclinical or clinical trials against these autophagy related diseases, especially cancer. Small molecule vacuolin-1 potently and reversibly inhibits both endosomal-lysosomal trafficking and autophagosome-lysosome fusion, yet the molecular mechanisms underlying vacuolin-1 mediated autophagy inhibition remain unknown. Here, we first performed the virtual drug screening and identified 14 vacuolin-1 analogues as autophagy inhibitors. Based on these virtual screening results, we further designed and synthesized 17 vacuolin-1 analogues, and found that 13 of them are autophagy inhibitors and a couple of them are as potent as vacuolin-1. In summary, these studies expanded the pool of useful autophagy inhibitors and reveal the structural-activity relationship of vacuolin-1 analogues, which is useful for future development of vacuolin-1 analogues with high potency and for identification of the molecular targets of vacuolin-1.
Synthesis and structure of new 1,3,5-triazine-pyrazole derivatives
Mikhaylichenko, Svetlana N.,Patel, Saurabh M.,Dalili, Shadi,Chesnyuk, Aleksey A.,Zaplishny, Vladimir N.
body text, p. 2505 - 2508 (2009/09/05)
We have studied the reaction of methylenedicarbonyl compounds with 4,6-disubstituted 2-hydrazinyl-1,3,5-triazine in order to obtain novel coupled biheterocyclic aromatic systems with potential bioactivity. Reaction conditions were studied and optimized, a
