One-pot two-step catalytic synthesis of 6-amino-2-pyridone-3,5-dicarbonitriles enabling anti-cancer bioactivity.

Autor:	Nicely LG; Department of Cellular and Systems Medicine, School of Medicine, University of Dundee Dundee DD1 9SY UK s.y.banerjee@dundee.ac.uk., Vala RM; Department of Chemistry, Sardar Patel University Vallabh Vidyanagar 388120 Gujarat India hm_patel@spuvvn.edu., Upadhyay DB; Department of Chemistry, Sardar Patel University Vallabh Vidyanagar 388120 Gujarat India hm_patel@spuvvn.edu., Nogales J; Department of Cellular and Systems Medicine, School of Medicine, University of Dundee Dundee DD1 9SY UK s.y.banerjee@dundee.ac.uk., Chi C; Department of Medical Biochemistry and Microbiology, Uppsala University SE-75123 Uppsala Sweden., Banerjee S; Department of Cellular and Systems Medicine, School of Medicine, University of Dundee Dundee DD1 9SY UK s.y.banerjee@dundee.ac.uk., Patel HM; Department of Chemistry, Sardar Patel University Vallabh Vidyanagar 388120 Gujarat India hm_patel@spuvvn.edu.
Jazyk:	angličtina
Zdroj:	RSC advances [RSC Adv] 2022 Aug 24; Vol. 12 (37), pp. 23889-23897. Date of Electronic Publication: 2022 Aug 24 (Print Publication: 2022).
DOI:	10.1039/d2ra03579k
Abstrakt:	We report a one-pot two-step synthesis of a bioactive 6-amino-2-pyridone-3,5-dicarbonitrile derivative using natural product catalysts betaine and guanidine carbonate. Anti-cancer bioactivity was observed in specific molecules within the library of 16 derivatives. Out of the compounds, 5o had the most potent anti-cancer activity against glioblastoma cells and was selected for further study. Compound 5o showed anti-cancer properties against liver, breast, lung cancers as well as primary patient-derived glioblastoma cell lines. Furthermore, 5o in combination with specific clinically relevant small molecule inhibitors induced enhanced cytotoxicity in glioblastoma cells. Through our current work, we establish a promising 6-amino-2-pyridone-3,5-dicarbonitrile based lead compound with anti-cancer activity either on its own or in combination with specific clinically relevant small molecule kinase and proteasome inhibitors. Competing Interests: The authors declare no conflicts of interest. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu