Results in Chemistry (Jan 2024)
A multifaceted approach for the development of novel Hantzsch 1,4-dihydropyridines as anticancer agents: Rational design, parallel synthesis, analysis, cytotoxicity and EGFR/HER2 inhibition studies
Abstract
Dihydropyridines (DHPs) exhibit a wide range of pharmacological properties especially against cancer. In this context, a new series of 1,4-dihydropyridines were meticulously designed employing scaffold hybridization technique targeting the EGFR/HER2 receptors. The parallel synthesis of the designed dihydropyridines was achieved using the Hantzsch multiple component reactions. Following the synthesis, rigorous purification methods were carried out and elucidation of their chemical structures through comprehensive analytical techniques such as IR, NMR, and Mass Spectrometry. The initial synthetic step of acetoacetanilide formation was of less product yield contrasting with the satisfactory yields achieved for final multicomponent reactions. The synthesized ligands were subjected to screening against MCF-7 breast cancer and normal Vero cells to evaluate their potential anti-cancer activity. This assessment was carried out by quantifying cytotoxicity levels and structure activity relationships. Among them, compounds 6 and 14 exhibited the good inhibitory effects on the proliferation of MCF-7 cells with an IC50 value of 14.44 and 14.38 μM, respectively, which was quite closer to that of Lapatinib. Furthermore, the influence of ligands on target proteins expressions were assessed via flow cytometry experiments against EGFR & HER2. Computational studies were also performed to correlate the experimental results.
