Synthesis and biological evaluation of N, N-dialkylcarboxy coumarin-NO donor conjugates as potential anticancer agents
| Autor: | Conor T. Ronayne, Jon N. Rumbley, Hithardha Palle, Shirisha Jonnalagadda, Lucas N. Solano, Tanner J. Schumacher, Zachary S. Gardner, Venkatram R. Mereddy, Chinnadurai Mani, Sravan K. Jonnalagadda, Grady L. Nelson |
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| Rok vydání: | 2021 |
| Předmět: |
Clinical Biochemistry
Pharmaceutical Science Antineoplastic Agents Apoptosis Nitric Oxide Biochemistry chemistry.chemical_compound Mice Structure-Activity Relationship In vivo Coumarins Cell Line Tumor Drug Discovery medicine Animals Humans Molecular Biology Cell Proliferation Dose-Response Relationship Drug Molecular Structure Organic Chemistry Furoxan Cancer Coumarin medicine.disease In vitro chemistry Cell culture Cancer cell Molecular Medicine Female Drug Screening Assays Antitumor |
| Zdroj: | Bioorganicmedicinal chemistry letters. 52 |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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