2. Academic Validation
  3. Novel indazole skeleton derivatives containing 1,2,3-triazole as potential anti-prostate cancer drugs

Novel indazole skeleton derivatives containing 1,2,3-triazole as potential anti-prostate cancer drugs

  • Bioorg Med Chem Lett. 2022 May 15:64:128654. doi: 10.1016/j.bmcl.2022.128654.
Yaquan Cao 1,  Yingxue Yang 1,  Maxwell Ampomah-Wireko 1,  Firas Obaid Arhema Frejat 1,  Hongjin Zhai 1,  Shuo Zhang 1,  Huanhuan Wang 1,  Pu Yang 1,  Qingyan Yuan 2,  Guanlian Wu 2,  Chunli Wu 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001, PR China.
  • 2 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001, PR China; Henan Qunbo Pharmaceutical Research Institute Co. LTD, Zhengzhou 450001, PR China.
  • 3 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001, PR China; Henan Qunbo Pharmaceutical Research Institute Co. LTD, Zhengzhou 450001, PR China. Electronic address: kedi2009@126.com.
PMID: 35259487 DOI: 10.1016/j.bmcl.2022.128654
Abstract

In this study, a novel batch of indazole containing 1,2,3-triazole agents were designed and synthesized. The antiproliferative activity of target compounds in four human Cancer cells, PC-3 (human prostate Cancer cell), MCF-7 (human breast Cancer cell), HepG-2 (human hepatoma cell) and MGC-803 (human gastric Cancer cell), was evaluated by thiazole blue (MTT). In the antiproliferative activity screening, we were surprised to find that most compounds have specific cytotoxicity to PC-3 Cancer cells. In particular, 9a has an IC50 value of 4.42 ± 0.06 μmol/L against PC-3 cell. Cloning experiments showed that 9a could inhibit the formation of PC-3 Cancer cell clone in a dose-dependent manner. Through cell cycle arrest experiment, we found that compound 9a can block the cell cycle in G2/M phase and inhibit cell proliferation. Finally, by evaluating the safety of compound 9a, we noticed that it showed fairly good safety both in vivo and in vitro. Overall, based on the biological activity evaluation and safety, analogue 9a can be viewed as a potential lead compound for further development of novel anti-prostate Cancer drug.

Keywords

1,2,3- triazole; Cancer; Indazole; Prostatic cancer; Specificity.

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