Synthesis and biological evaluation of N, N-dialkylcarboxy coumarin-NO donor conjugates as potential anticancer agents

Grady L. Nelson, Conor T Ronayne, Lucas N. Solano, Sravan K. Jonnalagadda, Shirisha Jonnalagadda, Tanner J. Schumacher, Zachary S. Gardner, Hithardha Palle, Chinnadurai Mani, Jon Rumbley, Venkatram R. Mereddy

Research output: Contribution to journalArticlepeer-review

Abstract

A series of nitric oxide (NO) donor furoxan conjugates of N, N-dialkylcarboxy coumarins have been synthesized as potential anticancer agents. The synthesized compounds have been tested for their in vitro antiproliferative activities on various cancer and noncancerous cell lines. The candidate derivatives exhibit selectivity towards cancer cells with excellent activities in low nM to µM concentrations. In vitro mechanistic studies indicate that the candidate compounds generate substantial NO, inhibit colony formation, and cause apoptosis in cancer cells. A preliminary in vivo tolerance study of the lead candidate 10 in mice indicates that it is well-tolerated, evidenced by zero mortality and normal body weight gains in treated mice. Further translation of the lead derivative 10 using MDA-MB-231 based tumor xenograft model shows good tumor growth reduction.

Original languageEnglish (US)
Article number128411
JournalBioorganic and Medicinal Chemistry Letters
Volume52
Early online dateOct 6 2021
DOIs
StatePublished - Nov 15 2021

Bibliographical note

Funding Information:
We thank the Department of Chemistry and Biochemistry, University of Minnesota Duluth, College of Pharmacy and Integrated Biosciences, University of Minnesota, Randy Shaver Cancer Research and Community Fund, Whiteside Clinical Research Institute for their financial support.

Publisher Copyright:
© 2021 Elsevier Ltd

Keywords

  • Diphenylsulfonylfuroxan
  • N N-dialkylcarboxy coumarin
  • NO donor
  • Triple-negative breast cancer

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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