Synthesis and X‐Ray Structural Analyses Combined Anticancer Efficacy and Molecular Docking for N‐Aryl‐(2‐pyridyl)aldimines

Abstract

Abstract The reaction of 2‐amino‐4,6‐dimethylpyridine with 4 ‐ cyanobenzaldehyde, salicylaldehyde or 2‐hydroxy‐1‐naphthaldehyde furnished the corresponding N ‐aryl‐(2‐pyridyl)aldimines in very good yields. The synthetised Schiff bases were characterized by FT‐IR, 1 H, 13 C, DEPT‐135 and [ 1 H, 13 C]‐HSQC NMR spectroscopy, HRMS and elemental analyses. Additionally, the structure of 2‐(( E )‐(4,6‐dimethylpyridin‐2‐ylimino)methyl)phenol was unambiguously determined by single crystal X‐ray diffraction analysis. Hirshfeld analysis of molecular packing was performed. The most common intermolecular interaction is the hydrogen‐hydrogen (56.8 %) contacts while the most significant interactions are the O…H (6.5 %) and C…C (4.2 %) contacts. DFT calculated geometric parameters and NMR chemical shifts are well correlated with the experimental data. This compound has a net dipole moment of 2.4261 Debye. The MCF‐7 growth was suppressed by N ‐aryl‐(2‐pyridyl)aldimines more than that for T47D cell line. The IC 50 values of 4‐(( E )‐(4,6‐dimethylpyridin‐2‐ylimino)methyl)benzonitrile against MCF‐7 and T47D cell lines were the lowest and it is considered the most promising candidate as anticancer agent. Furthermore, this study conducted a molecular docking of benzonitrile‐based Schiff base onto DNA duplex to explore a potential molecular mechanism for the robust anticancer activities of this Schiff base adduct. The molecular docking results indicate that benzonitrile‐based Schiff base exhibits characteristics of a potential DNA minor groove binder.