Nicely Lynden G, Vala Ruturajsinh M, Upadhyay Dipti B, Nogales Joaquina, Chi Celestine, Banerjee Sourav, Patel Hitendra M
Department of Cellular and Systems Medicine, School of Medicine, University of Dundee Dundee DD1 9SY UK
Department of Chemistry, Sardar Patel University Vallabh Vidyanagar 388120 Gujarat India
RSC Adv. 2022 Aug 24;12(37):23889-23897. doi: 10.1039/d2ra03579k. eCollection 2022 Aug 22.
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.
我们报道了一种使用天然产物催化剂甜菜碱和碳酸胍一锅两步合成生物活性6-氨基-2-吡啶酮-3,5-二腈衍生物的方法。在16种衍生物的文库中的特定分子中观察到了抗癌生物活性。在这些化合物中，5o对胶质母细胞瘤细胞具有最强的抗癌活性，并被选作进一步研究。化合物5o对肝癌、乳腺癌、肺癌以及原发性患者来源的胶质母细胞瘤细胞系均显示出抗癌特性。此外，5o与特定的临床相关小分子抑制剂联合使用可增强胶质母细胞瘤细胞的细胞毒性。通过我们目前的工作，我们建立了一种有前景的基于6-氨基-2-吡啶酮-3,5-二腈的先导化合物，其自身或与特定的临床相关小分子激酶和蛋白酶体抑制剂联合使用时均具有抗癌活性。
