Design, synthesis and antitumor activities of thiazole-containing mitochondrial targeting agents

Dongdong Zhang, Yixin Hu, Zhiqiang Hao, Yang Zhang, Shuhua Luo, Xin Dang, Ran Sun, Shixin Duan, Dan Lv, Faqin Jiang, Lei Fu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


In this study, a novel batch of thiazole-containing mitochondrial targeting agents were designed and synthesized. Four kinds of mitochondrial targeting moieties and six kinds of linkers were designed. Their structures were confirmed by NMR and HR-MS. The screening of antiproliferative activity revealed that most compounds displayed cytotoxicity on HeLa cancer cell. In particular, D1 has an IC50 value of 35.32 μmol·L−1 against HeLa cell. In addition, cellular respiratory activities were also tested on HeLa cancer cells. D1 had a basal oxygen consumption rate of 8.84 pmol·s−1·mL−1. Also, D1 inhibited the mitochondrial respiration of HeLa cell significantly at 5 μmol·L−1, as well as a complete inhibitory of oxygen consumption for cellular ATP coupling. Furthermore, the pKa, logP, and logD under different pH conditions of all the compounds were calculated by the ACD/Percepta-PhysChem Suite, and the results manifested the correlation between physicochemical properties and chemical activity of compounds. The results identify D1 as a promising mitochondria inhibitor and anticancer agent with appropriate physicochemical properties.

Original languageEnglish
Article number105271
JournalBioorganic Chemistry
Publication statusPublished - Oct 2021
Externally publishedYes


  • Antitumor
  • Mitochondrial respiration
  • Mitochondrial targeting
  • Thiazole

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