Exploring Anticancer Activity and DNA Binding of Metal (II) Salicylaldehyde Schiff Base Complexes: A Convergence of Experimental and Computational Perspectives

ABSTRACT Metal complexes derived from salicylaldehyde‐based Schiff bases are among the frontrunners in the pursuit of precise and potent cancer treatments due to their remarkable prowess. In this study, salicylaldehyde‐based Schiff base ( HL ) was prepared via a reaction between 2‐amino‐5‐benzonitrile and salicylaldehyde. Subsequently, HL was further reacted with Ni (II), Co (II), Cu (II) and Pd (II) ions using their respective metal salts to obtain homoleptic mononuclear complexes ( C1 – C4 ). The composition of HL and C1 – C4 were determined using 1 H and 13 C NMR, UV–Vis, FTIR, CHN, SEM–EDX and HRMS analyses. In addition, the structural geometries of HL , C1 , C3 and C4 were determined in solid state using single crystal X‐ray diffraction analysis and corroborate with the mentioned characterization techniques employed. The stability of compounds was assessed through time‐dependent UV–vis spectroscopy, revealing that C2 exhibited the highest stability under the experimental conditions. Subsequently, the anticancer effects of HL and C2 were tested on breast cancer cell lines (MCF‐7) using MTT, LDH and ATP assays. Both HL and C2 displayed potential cytotoxicity on the MCF‐7 cell line, in which C2 displayed a better inhibition effect than a standard chemotherapeutic agent, doxorubicin (DOX), with IC 50 of 43.08 μM. We postulate that the mechanism by which C2 may function is by binding to DNA ( = 0.114 (± 0.02) × 10 4 ) and intercalation (shown by UV‐CD and UV‐LD spectroscopy) at the AT rich sites. These data were corroborated in silico by extra precision (XP) docking and molecular dynamic (MD) simulations.