Synthesis and Biological Evaluation of Telmisartan Alkylamine Derivatives as Potential Anticancer Agents

Tanner J. Schumacher, Zachary S. Gardner, Michael P. McParlan, Tasmin Omy, Komaraiah Palle, Jon Rumbley, Venkatram R. Mereddy

Research output: Contribution to journalArticlepeer-review


Background/Aim: Telmisartan is an angiotensin II receptor type 1 (AT1) antagonist with anticancer properties against solid and hematological cancer cell lines. Using telmisartan as a template, we developed alkylamine derivatives with reduced AT1 activity but increased anticancer activity. Materials and Methods: Synthesis of candidate compounds was carried out via hexafluorophosphate benzotriazole tetramethyl uronium coupling reaction, then their inhibition of cell proliferation was determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and colony-formation assay was carried out on the lead candidate compound 8. Cell death via apoptosis or necrosis by compound 8 was determined by flow cytometry using annexin V and propidium iodide, tolerability dosing was carried out in ICR mice, and tumor-reduction properties were determined in an MDA-MB-231 xenograft model. Results: Some of the synthesized candidates exhibited good inhibition of cell proliferation with low micromolar half maximal effective concentrations in triple-negative breast cancer cell lines MDA-MB-231 and 4T1. Compound 8 exhibited lower affinity towards AT1 than parent telmisartan, inhibition of colony formation, and cell-cycle analysis revealed apoptosis as potentially important in causing cell death. In vivo evaluation with compound 8 indicated that it was well tolerated at high concentrations in healthy mice. Additionally, compound 8 showed higher growth inhibition in the MDA-MB-231 tumor xenograft mouse model compared to telmisartan. Conclusion: Our study indicated that alkylamine derivatives of telmisartan exhibited good solubility and higher inhibition of cancer cell proliferation than telmisartan. Compound 8 was found to be a good lead compound, with potential for development as an anticancer agent.

Original languageEnglish (US)
Pages (from-to)911-919
Number of pages9
JournalAnticancer Research
Issue number3
StatePublished - Mar 2024

Bibliographical note

Publisher Copyright:
© 2024 International Institute of Anticancer Research. All rights reserved.


  • AT1 antagonist
  • MDA-MB-231
  • TNBC
  • alkylamine derivatives
  • telmisartan

PubMed: MeSH publication types

  • Journal Article


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