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

• Published in: Bioorganic & medicinal chemistry letters 2021-11, Vol.52, p.128411-128411, Article 128411
• Main 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.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Coumarins - chemistry; Coumarins - pharmacology; Diphenylsulfonylfuroxan; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Humans; Mice; Molecular Structure; N N-dialkylcarboxy coumarin; Nitric Oxide - chemistry; Nitric Oxide - pharmacology; NO donor; Structure-Activity Relationship; Triple-negative breast cancer
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2021.128411

[Display omitted] 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.