The anti-breast cancer activity of indeno[1,2-b]pyridin-5-one and their hydrazonal precursors endowed with anti-CDK-2 enzyme activity

Abstract

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.