2. Academic Validation
  3. Synthesis and biological evaluation of novel isothiazoloquinoline quinone analogues

Synthesis and biological evaluation of novel isothiazoloquinoline quinone analogues

  • Bioorg Med Chem Lett. 2020 Aug 15;30(16):127286. doi: 10.1016/j.bmcl.2020.127286.
Ling Chen 1,  Yuan-Zhu Xie 2,  Zhi-Yong Luo 2,  Li-Jun Liu 2,  Zi-Zheng Zou 2,  Hong-Dou Liu 2,  Fan-Rong Kong 2,  Ying Hao 1,  Jin-Lei Gao 1,  Liu-Liu Wang 1,  Da-You Ma 3,  Su-You Liu 4
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
  • 2 School of Life Sciences, Central South University, Changsha 410013, China.
  • 3 School of Pharmaceutical Sciences, Central South University, Changsha 410013, China. Electronic address: madayou@hotmail.com.
  • 4 School of Pharmaceutical Sciences, Central South University, Changsha 410013, China. Electronic address: suyouliu@csu.edu.cn.
PMID: 32631508 DOI: 10.1016/j.bmcl.2020.127286
Abstract

Natural Quinones and their analogues have attracted growing attention because of their novel Anticancer activities. A series of novel isothiazoloquinoline quinone analogues were synthesized and evaluated for antitumor activities against four different kind of Cancer cells. Among them, isothiazoloquinolinoquinones inhibited Cancer cells proliferation effectively with IC50 values in the nanomolar range, and isothiazoloquinolinoquinone 13a induced the cell Apoptosis. Further exploration of possible mechanism of action indicates that 13a not only activates ROS production through NQO1-directed redox cycling but also inhibits the phosphorylation of STAT3. These findings indicate that 13a has potential use for the development of new skeleton drug candidate as an efficient substrate of NQO1 and STAT3 Inhibitor.

Keywords

Antitumor activities; Isothiazoloquinoline quinone analogues; NQO1 substrate; ROS production; STAT3 inhibitor; Structure–activity relationship; Synthesis.

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