Synthesis and biological evaluation of N, N-dialkylcarboxy coumarin-NO donor conjugates as potential anticancer agents. (15th November 2021)

• Record Type: Journal Article
• Authors: Nelson, Grady L.; Ronayne, Conor T.; Solano, Lucas N.; Jonnalagadda, Sravan K.; Jonnalagadda, Shirisha; Schumacher, Tanner J.; Gardner, Zachary S.; Palle, Hithardha; Mani, Chinnadurai; Rumbley, Jon; Mereddy, Venkatram R.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 52(2021)
• Publication Date: 2021-11-15
• Subjects: N N-dialkylcarboxy coumarin -- Diphenylsulfonylfuroxan -- NO donor -- Triple-negative breast cancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.128411
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.