Synthesis, characterization, biological evaluation, and molecular docking approach of nickel (II) complexes containing O, N‐donor chelation pattern of sulfonamide‐based Schiff bases

Abstract

A series of Schiff bases (L1–L4) that possess in their structure bioactive sulfonamide group and their nickel (II) complexes have been synthesized. Microanalytical analyses, various spectroscopic methods such as Fourier transform infrared spectroscopy (FT‐IR), 1H nuclear magnetic resonance (NMR), 13C NMR, UV–Vis, and MS, are used to explore the nature of bonding and to elucidate the chemical structures. The analytical and magnetic values suggest a range of stoichiometries 1:1, 1:2, and 2:1 (M:L) for the synthesized complexes of almost square planar geometry. The spectral comparative interpretation reveals that L1 and L2 coordinate to the central Ni (II) in tetradentate ONON donor sequence, whereas L3 and L4 in bidentate ON pattern through deprotonated phenolic‐O and the azomethine‐N. Density functional theory (DFT) and MOE‐docking approaches are used to evaluate the molecular parameters and the binding propensity of the synthesized ligands and their complexes with 3s7s protein and to signify their inhibition strength. Besides, the anticancer, antimicrobial and antifungal activities have been screened against number of tumor cells and human pathogen strains. These in vitro studies reveal that Schiff base L4 and its complex, [Ni(L4‐H)(OAc)(H2O)], have superior activities reflecting the importance of inserting bioactive pendant substituents such as thiazole ring and 3‐fluorophenylazo to the pharmacophoric sulfonamide moiety. Moreover, some of the synthesized Ni (II) complexes display promising therapeutic effects as novel non‐platinum antitumor agents after further preclinical investigations.

Designing metal chelates of halogenated sulfonamide Schiff bases as potent nonplatinum anticancer drugs using spectroscopic, molecular docking and biological studies

“…The chemical reactivity of the synthesized Schiff bases was predicted from the energy difference between the low unoccupied (LUMO) and the high occupied molecular orbitals (HOMO) of the corresponding ligand, E (Fig. 13) 8 . Noticeably, there is a good correlation between the structure of synthesized ligands and their reactivity.…”

“…Effectively short H-bond was observed in most of the docked protein-ligand complexes. As an example, the interaction of SB 1 and SB 4 through O (27) with ARG 115 amino acid and O(9) with ARG 435 amino acid respectively, displayed bond lengths that are less than 3.5 Å 8,48 . Worth mentioning that the negative values of the binding energies (Table 4) indicate spontaneous interaction with the protein.…”

“…1) as deduced in the antimicrobial Sect. 8,55 . Interestingly, SB 5 (6.32 μM) exhibited threefold inhibition efficacy more than cisplatin recommending it as a promising breast anticancer drug and in accord with US NCI program (IC 50 < 10 μM) 57 www.nature.com/scientificreports/ Furthermore, a comparative study was also made to compare the cytotoxicity of some ligands (SB 1 and SB 2 ) against different human cell lines HCT-116 (colon carcinoma), HepG-2 (hepatocellular carcinoma), and MCF-7 (breast carcinoma) (Figs.…”

“…The activity of these heterocyclic compounds against wide varieties of pathogens increases especially when introduced in the form of metal complexes 4,5 . Transition metal complexes of Schiff bases derived from sulfa drugs are among systems that have been reported extensively for their pronounced medicinal performance [5][6][7][8] . Most of the sulfa drugs exhibit a bacteriostatic effect by preventing cell division through the inhibition of the dihydropteroate synthase enzyme that is essential in the proteins and nucleic acids formation in bacterial cells 9,10 .…”

Synthesis, Physicochemical Characterization, Biological Assessment, and Molecular Docking Study of Some Metal Complexes of Alloxan and Ninhydrin as Alterdentate Ligands

“…Nevertheless, the involvement of ninhydrin in the isolation of mononuclear metal complexes is rare in the literature [ 19 , 20 ]. Besides, there is increasing attention to designing and developing novel non-platinum metal complexes to overcome the unsolved clinical problems combined with platinum-based chemical drugs [ 21 , 22 ]. In continuation, the main objective of this research aims to prepare a series of metal complexes derived from alloxan or ninhydrin for diverse applications in the hope of innovating low-cost anti-pathogenic or anticancer candidates and overcoming the problems associated with the use of existing therapeutics.…”