2. Academic Validation
  3. Synthesis and anticancer activity evaluation of naphthalene-substituted triazole spirodienones

Synthesis and anticancer activity evaluation of naphthalene-substituted triazole spirodienones

  • Eur J Med Chem. 2021 Mar 5:213:113039. doi: 10.1016/j.ejmech.2020.113039.
Lan Luo 1,  Jing Jing Jia 1,  Qiu Zhong 2,  Xue Zhong 1,  Shilong Zheng 3,  Guangdi Wang 4,  Ling He 5
Affiliations

Affiliations

  • 1 Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 610041, China.
  • 2 Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. Electronic address: qzhong@xula.edu.
  • 3 Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. Electronic address: szheng@xula.edu.
  • 4 Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. Electronic address: gwang@xula.edu.
  • 5 Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 610041, China. Electronic address: heling2012@scu.edu.cn.
PMID: 33261898 DOI: 10.1016/j.ejmech.2020.113039
Abstract

Building on our previous work that discovered 1,2,4-triazole-spirodienone as a promising pharmacophore for Anticancer activity, we have further diversified 1,2,4-triazole- spirodienone derivatives and synthesized a series of novel naphthalene-substituted triazole spirodienones to explore their antineoplastic activity. Of these, compound 6a possesses remarkable in vitro cytotoxic activity by arresting cell cycle and inducing Apoptosis in MDA-MB-231 cells. Subsequently, acute toxicity assay showed that 6a at 20 mg/kg has no apparent toxicity to the major organ in mice. In addition, compound 6ain vivo suppressed breast Cancer 4T1 tumor growth. Taken together, these results indicate that compound 6a may be a potential Anticancer agent for further development.

Keywords

4T1 breast tumor; Anti-proliferation; Cytotoxicity; MDA-MB-231; Naphthalene-substituted triazole spirodienones.

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