Syntheses of novel 1,2,3-triazole-based Schiff base ligands and their Co(II) complexes: DNA/BSA binding, DNA cleavage, topoisomerase IIα inhibition and cytotoxicity studies

In this study, three novel cobalt(II) complexes [Co(HL^1–3)₂]were synthesized from Schiff base ligands bearing 1,2,3-triazole and oxime functional groups and their structures were elucidated by FTIR, UV–Vis spectroscopy, Molar conductivity, Magnetic moment measurements, MALDI-TOF-MS and elemental analyses. Single-crystal X-ray diffraction analysis of oxidised [Co(HL¹)L¹] confirmed the octahedral geometry of the complex with triclinic P -1 space group. The Hirshfeld surface analysis showed that the hydrogen bonding and van der Waals interactions were dominant in the crystal. The interactions of the complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were investigated using UV–Vis, fluorescence spectroscopy and viscometry. The data suggested minor groove binding with partial intercalation, supported by moderate binding constants (K_b ∼ 10⁴ M⁻¹) and FRET distances (r < 4.5 nm). DNA cleavage studies revealed the time- and concentration-dependent activities under hydrolytic and oxidative conditions, with [Co(HL¹)₂] showing rapid and efficient cleavage. Radical scavenging assays indicated the involvement of reactive oxygen species and EDTA inhibition confirmed a metal-centered mechanism. Topoisomerase IIα inhibition assays showed that the complexes act as catalytic inhibitors with [Co(HL³)₂] exhibiting the strongest inhibition. MTT assays against Caco-2, MDA-MB-231 and LNCaP cancer cell lines revealed that [Co(HL³)₂] demonstrated the highest cytotoxicity, especially against Caco-2 cells, with lower toxicity toward normal HEK-293 cells. Findings highlight [Co(HL³)₂] as a promising candidate for further development as a multi-target anticancer agent.