A new series of aza-indeno[1,2-b]pyridin-5-one derivatives 6a-h was designed. The novel pyridin-5-one derivatives were constructed via cyclization of their corresponding hydrazonal precursors 4a-h with indandione. Structural elucidation of all new compounds. was fully conducted. All novel hydrazonals 4a-h and indeno-pyridinone derivatives 6a-h were screened for their anti-breast cancer activity against two cell lines; MCF-7 and MDA-231. Among all screened compounds, hydrazonals 4a and 4h showed the highest cytotoxic potency. The cell cycle analysis data revealed that hydrazonals 4a and 4h caused a 1.36- and 1.2-fold increase in the proportion of cells in S phase. Annexin V-FITC apoptosis test for the same two hydrazonal derivatives 4a and 4h indicated that these molecules induce apoptosis by means of the programmed cell death pathway rather than the necrotic pathway. Pharmacokinetic parameters of these two hydrazonals as well as their molecular docking study with the CDK-2 enzyme, provided more insights of their biological activity and druggability.

设计了一系列新的氮杂茚并[1,2- b ]吡啶-5-酮衍生物6a-h 。新型吡啶-5-酮衍生物是通过其相应的腙前体4a-h与茚满二酮环化而构建的。所有新化合物的结构阐明。已全面进行。筛选了所有新型腙醛4a-h和茚并吡啶酮衍生物6a-h对两种细胞系的抗乳腺癌活性；MCF-7 和 MDA-231。在所有筛选的化合物中，腙4a和4h显示出最高的细胞毒性效力。细胞周期分析数据显示腙4a和4h导致S期细胞比例增加1.36倍和1.2倍。对相同的两种腙衍生物4a和4h的Annexin V-FITC细胞凋亡测试表明，这些分子通过程序性细胞死亡途径而不是坏死途径诱导细胞凋亡。这两种腙的药代动力学参数以及它们与 CDK-2 酶的分子对接研究，为它们的生物活性和成药性提供了更多见解。