Coumarin carboxylic acids as monocarboxylate transporter 1 inhibitors: In vitro and in vivo studies as potential anticancer agents

Shirisha Gurrapu, Sravan K. Jonnalagadda, Mohammad A. Alam, Conor T. Ronayne, Grady L. Nelson, Lucas N. Solano, Erica A. Lueth, Lester R Drewes, Venkatram R Mereddy

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Novel N,N-dialkyl carboxy coumarins have been synthesized as potential anticancer agents via inhibition of monocarboxylate transporter 1 (MCT1). These coumarin carboxylic acids have been evaluated for their in vitro MCT1 inhibition, MTT cancer cell viability, bidirectional Caco-2 cell permeability, and stability in human and liver microsomes. These results indicate that one of the lead candidate compounds 4a has good absorption, metabolic stability, and a low drug efflux ratio. Systemic toxicity studies with lead compound 4a in healthy mice demonstrate that this inhibitor is well tolerated based on zero animal mortality and normal body weight gains compared to the control group. In vivo tumor growth inhibition studies in mice show that the candidate compound 4a exhibits significant single agent activity in MCT1 expressing GL261-luc2 syngraft model but doesn't show significant activity in MCT4 expressing MDA-MB-231 xenograft model, indicating the selectivity of 4a for MCT1 expressing tumors.

Original languageEnglish (US)
Pages (from-to)3282-3286
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number14
StatePublished - 2016

Bibliographical note

Funding Information:
This work was supported by University of Minnesota Duluth; Department of Defense Breast Cancer Research Proposal, Breakthrough Award W81XWH-15-1-0047; Whiteside Clinical Research Institute, Duluth, Minnesota; Center for Pharmaceutical Development, University of Minnesota; Minnesota Partnership for Biotechnology & Medical Genomics; Masonic Cancer Center Brainstorm Mechanism, University of Minnesota; and KAM and Bighley Foundation, University of Minnesota.


  • GL261-luc2
  • Glioblastoma
  • MCT
  • MDA-MB-231
  • Monocarboxylate transporter 1
  • N,N-Dialkyl carboxy coumarin
  • Triple negative breast cancer
  • Tumor glycolysis

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