Identification of Novel Vacuolin-1 Analogues as Autophagy Inhibitors by Virtual Drug Screening and Chemical Synthesis

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

5 Scopus Citations
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Author(s)

  • Chang Chen
  • Yingying Lu
  • Ho Ming Siu
  • Jintao Guan
  • Longchao Zhu
  • Shuang Zhang
  • Liangren Zhang

Detail(s)

Original languageEnglish
Journal / PublicationMolecules
Volume22
Issue number6
Publication statusPublished - 27 May 2017

Link(s)

Abstract

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.

Research Area(s)

  • Autophagy, Inhibitor, LC3B-II, SAR, Vacuolin-1

Citation Format(s)

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.

In: Molecules, Vol. 22, No. 6, 27.05.2017.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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