Synthesis, in vitro, and in vivo evaluation of novel N-phenylindazolyl diarylureas as potential anti-cancer agents

Lucas N. Solano, Grady L. Nelson, Conor T. Ronayne, Shirisha Jonnalagadda, Sravan K. Jonnalagadda, Kaija Kottke, Robert Chitren, Joseph L. Johnson, Manoj K. Pandey, Subash C. Jonnalagadda, Venkatram R. Mereddy

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Novel N-phenylindazole based diarylureas have been designed, synthesized and evaluated as potential anticancer agents. In vitro cell viability studies of these derivatives illustrate good potency with IC50 values in the range of 0.4–50 μM in several cancer cell lines including murine metastatic breast cancer 4T1, murine glioblastoma GL261, human triple negative breast cancer MDA-MB-231, human pancreatic cancer MIAPaCa-2, and human colorectal cancer cell line WiDr. The ester group in the lead compound 8i was modified to incorporate amino-amides to increase solubility and stability while retaining biological activity. Further in vitro studies reveal that lead candidates inhibit tube length in HUVEC cells. In vivo systemic toxicity studies indicate that these candidate compounds are well tolerated in mice without any significant side effects. Anticancer efficacy studies in WiDr tumor xenograft and 4T1 tumor syngraft models demonstrate that the lead candidate 11 exhibits significant antitumor properties as a single agent in these tumor models.

Original languageEnglish (US)
Article number17969
JournalScientific reports
Issue number1
StatePublished - Dec 1 2020

Bibliographical note

Funding Information:
This work was supported by University of Minnesota Duluth; Whiteside Clinical Research Institute, Minnesota, and Randy Shaver Cancer Research and Community Fund, Minnesota.

Publisher Copyright:
© 2020, The Author(s).


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