Evaluation of anticancer activities, apoptosis, molecular docking, and antioxidant studies of new Ni(II), VO(IV), Cu(II) and Co(III) Schiff base complexes

Abstract

New Schiff base complexes have been synthesized via appropriate conventional methods using 2-ethoxy-6-(E)-[(prop-2-em-1-yl)imino]methylphenol (HL) as a Schiff base ligand. The compounds obtained were characterized by spectral analysis and X-ray diffraction. Recrystallization from methanol provided single crystals with rod-shaped (1) and rhombus-shaped (2) shapes. The complexes were found to be composed of NiL2 and (VO)L2, with the anionic ligand L- acting as a bidentate ligand, coordinating to metal centers via imino N and hydroxyl oxygen atoms in all cases. Compound (1) crystallizes in the orthorhombic system with the Pccn space group, while compound (2) crystallizes in the monoclinic system with the P21/n space group. Cyclic voltammetry experiments in DMF show a metal-centered reduction peak at (−1.23), (−1.32), (−0.82, 1.36), and (−0.61, −1.55) V, corresponding to the Ni II/NiI, VO2+/VO+, CuII/CuI, and CoIII/II-CoII/I, respectively. The complexes were evaluated for anticancer activity in a human tumor cell line (HT-29). 5-fluorouracil was used as a standard drug. All tested compounds of Schiff base ligand and complexes (1–4) showed anticancer activity with inhibitory concentration (IC50) values of 85.28(HL), 15.13(1), 10.83(2), 28.53(3) and 30.21(4) (μM), respectively. The in vitro cytotoxicity screening results revealed that all compounds showed promising activity against colorectal cancer. In particular, compounds (1) and (2) showed excellent activity against tumor cell lines. The antioxidant activity of the synthesized Schiff base was determined using the DPPH method (1, 1-diphenyl-2- picryl hydrazyl). The effective concentration (EC50) indicates that all compounds have good antioxidant activity (EC50 = 143.02(HL), 168.03(1), 27.31(2), 160.3(3) and 173.41(4). The biological activity spectra of synthesized compounds are predicted by the Pass Online Web Resource. In addition to the PASS program's prediction, molecular docking studies were also performed to find bind affinity to protein cyclooxygenase inhibitor (the structure PDB code 1CX2).