Synthesis, Structural Investigations, Molecular Docking, and Anticancer Activity of Some Novel Schiff Bases and Their Uranyl Complexes

Abstract

Three novel 2-aminopyrazine Schiff bases derived from salicylaldehyde derivatives and their uranyl complexes were synthesized and characterized by elemental analysis, UV-vis, FTIR, molar conductance, and thermal gravimetric analysis (TGA). The proposed structures were optimized using density functional theory (DFT/B3LYP) and 6–311G ∗(d,p) basis sets. All uranyl complexes are soluble in DMSO and have low molar conductance, which indicates that all the complexes are nonelectrolytes. The DNA binding of those Schiff bases and their uranyl complexes was studied using UV-vis spectroscopy, and screening of their ability to bind to calf thymus DNA (CT-DNA) showed that the complexes interact with CT-DNA through an intercalation mode, for which the Kb values ranged from 1 × 106 to 3.33 × 105 M−1. The anticancer activities of the Schiff base ligands and their uranyl complexes against two ovarian (Ovcar-3) and melanoma cell lines (M14) were investigated, and the results indicated that uranyl complexes exhibit better results than the Schiff base ligands. Molecular docking identified the distance, energy account, type, and position of links contributing to the interactions between these complexes and two different cancer proteins (3W2S and 2OPZ).

Synthesis, Spectroscopic Characterization and Biological Studies of Mn(II), Cu(II), Ni(II), Co(II) and Zn(II) Complexes with New Schiff Base of 2-((Pyrazine-2-ylimino)methyl)phenol

“…The 1 HNMR spectrum of the Schiff base has discussed in detail in our previous work [12]. The signal at 12.38 ppm in the free ligand indicated the presence of phenolic-OH proton has disappeared in the Zn(II) complex spectrum and confirmed the coordination by phenolic oxygen to the zinc ion.…”

“…In addition, the Schiff base shows another signal at 9.52 ppm which can be ascribed to the azomethine proton (-CH=N). This signal was shifted to 10.22 ppm after complexing to Zn(II) ion and reveals the involvement of azomethine nitrogen in the coordination of the zinc complex [12]. The 1 H NMR data for the ligand and Zn(II) are shown in Figure S2 and summarized in Table S2.…”

“…The observed sharp band of the pyrazine ring (C=N) in the ligand at 1561 cm −1 was shifted more than 5 cm −1 in the metal complexes, except the Cu(II), Table S1. This indicates that the pyrazine ring is involved in coordinating to the metal ions [12]. New broadband in three metal complexes Cu(II), Mn(II) and Ni(II) at 3334, 3315 and 3457 cm −1 could assign to ν(H 2 O) [22].…”

“…A sharp (C=N) band of the azomethine group was observed 1602 cm −1 in the free ligand [12]. After complexation, the vibration band of the azomethine group was decreased in intensity and shifted toward a lower frequency about 16-60 cm −1 in the metal complexes, except the Cu(II) complex that has low intensity band and shifted toward higher frequency about 2 cm −1 .…”

“…The Schiff base ligand that prepared by previous work [12]. Briefly, 2 mmol or 1 mmol of ligand was dissolved in absolute ethanol in 25 mL and adjusted with a drop of NaOH.…”