Indole-based NNN donor Schiff base ligand and its complexes: Sonication-assisted synthesis, characterization, DNA binding, anti-cancer evaluation and in-vitro biological assay

Abstract

A novel indole based NNN donor Schiff base ligand and its Ni(II), Zn(II) and Cd(II) complexes have been synthesized using sonication-assisted method which is a highly efficient eco-friendly mechanism. The synthesized complexes have been characterized using elemental analysis, UV-Vis spectroscopy, mass spectrometry, FT-IR, and NMR and are optimized using DFT approach, which provided their theoretical framework. The stoichiometry between the ligand and the metal ions was also determined using Job's method. The thermogravimetric (TGA/DSC) analyses confirm the stability for all complexes at room temperature followed by thermal decomposition in different steps. DNA binding activities have been assessed by employing UV-visible and fluorescence spectra using the CT-DNA. The estimated intrinsic binding constant (K_b) for NiL, ZnL, and CdL complexes was 6.00 × 10⁵, 5.58 × 10⁵, and 4.7 × 10⁵, respectively. In accordance with the K_b value, the quenching constant (K_sv) values of NiL, ZnL, and CdL are 5.59 × 10⁵ M^-1, 4.3 × 10⁵ M^-1, and 4.08 × 10⁵ M^-1 respectively. The anticancer properties have been assessed using MTT Assay. It has been found that the Ni(II) complex (NiL) is the most potent among the series with IC₅₀ of 169 µg/mL. An in-vitro antioxidant experiment using DPPH was used to evaluate the synthesizedcomplexes' ability to scavenge free radicals. The findings indicated that the complexes exhibited notable antioxidant properties. The antioxidant property ZnL has been found to be the highest with an IC₅₀ of 2.91 µg/mL and it follows the order is ZnL > NiL > CdL > L. Using the egg albumin denaturation technique, the anti-inflammatory property have been assessed, and the amount of protein denaturation inhibition has been computed. NiL has the highest % inhibition among the series studied. Comparatively, the metal complexes have been reported to exhibit higher biological activities than the prepared Schiff base ligand. The reason for the excellent biological properties observed in the metal complexes could be attributed to the incorporation of the electron-withdrawing CH₃COO^- during complexation. Molecular docking studies have been performed on the 2GYT protein and it has been found that the complexes have excellent binding affinity, with NiL having the lowest binding energy of -6.93 Kcal mol^-1. The values suggested that NiL is more effective against HePG2 cancer cells, which is also in accordance with the MTT Assay results.

Keywords: Anti-inflammatory; Anticancer; Antioxidant; DNA binding studies; Molecular docking.