Synthesis, DFT Calculations, Antiproliferative, Bactericidal Activity and Molecular Docking of Novel Mixed-Ligand Salen/8-Hydroxyquinoline Metal Complexes

Abstract

Despite the common use of salens and hydroxyquinolines as therapeutic and bioactive agents, their metal complexes are still under development. Here, we report the synthesis of novel mixed-ligand metal complexes (MSQ) comprising salen (S), derived from (2,2′-{1,2-ethanediylbis[nitrilo(E) methylylidene]}diphenol, and 8-hydroxyquinoline (Q) with Co(II), Ni(II), Cd(II), Al(III), and La(III). The structures and properties of these MSQ metal complexes were investigated using molar conductivity, melting point, FTIR, 1H NMR, 13C NMR, UV–VIS, mass spectra, and thermal analysis. Quantum calculation, analytical, and experimental measurements seem to suggest the proposed structure of the compounds and its uncommon monobasic tridentate binding mode of salen via phenolic oxygen, azomethine group, and the NH group. The general molecular formula of MSQ metal complexes is [M(S)(Q)(H2O)] for M (II) = Co, Ni, and Cd or [M(S)(Q)(Cl)] and [M(S)(Q)(H2O)]Cl for M(III) = La and Al, respectively. Importantly, all prepared metal complexes were evaluated for their antimicrobial and anticancer activities. The metal complexes exhibited high cytotoxic potency against human breast cancer (MDA-MB231) and liver cancer (Hep-G2) cell lines. Among all MSQ metal complexes, CoSQ and LaSQ produced IC50 values (1.49 and 1.95 µM, respectively) that were comparable to that of cisplatin (1.55 µM) against Hep-G2 cells, whereas CdSQ and LaSQ had best potency against MDA-MB231 with IC50 values of 1.95 and 1.43 µM, respectively. Furthermore, the metal complexes exhibited significant antimicrobial activities against a wide spectrum of both Gram-positive and -negative bacterial and fungal strains. The antibacterial and antifungal efficacies for the MSQ metal complexes, the free S and Q ligands, and the standard drugs gentamycin and ketoconazole decreased in the order AlSQ > LaSQ > CdSQ > gentamycin > NiSQ > CoSQ > Q > S for antibacterial activity, and for antifungal activity followed the trend of LaSQ > AlSQ > CdSQ > ketoconazole > NiSQ > CoSQ > Q > S. Molecular docking studies were performed to investigate the binding of the synthesized compounds with breast cancer oxidoreductase (PDB ID: 3HB5). According to the data obtained, the most probable coordination geometry is octahedral for all the metal complexes. The molecular and electronic structures of the metal complexes were optimized theoretically, and their quantum chemical parameters were calculated. PXRD results for the Cd(II) and La(III) metal complexes indicated that they were crystalline in nature.

Synthesis, characterization, potential antimicrobial, antioxidant, anticancer, DNA binding, and molecular docking activities and DFT on novel Co(II), Ni(II), VO(II), Cr(III), and La(III) Schiff base complexes

“…X‐ray powder diffraction analysis was performed on diffractometer Bruker D8 Advance using monochromatic Cu‐kα radiation( k = 1.5406 Å). The crystallite size D could be calculated using Scherrer's equation as follows [ 12,43 ] : where λ = 1.5406 Å, θ is the Bragg diffraction angle, K is a constant related to the crystallite shape (normally taken as 0.9), and β is the FWHM of the peak.…”

“…The reaction mixture was then refluxed at 60 C under stirring for 2 h. The resulting reaction product was filtered off from the reaction mixture, thoroughly washed with ethanol to remove any traces of the unreacted starting materials, and dried under vacuum. [12,43] The purities of the complexes were checked by thin-layer chromatography (TLC), and the yields and characterization details of the complexes were obtained, as shown in Table 1.…”

“…A thermal analysis (TG/DTG) was performed using a Shimadzu DTA/TG-50 thermal analyzer with a heating rate of 10 C/min in a nitrogen atmosphere with a flowrate of 20 ml/min, where platinum crucibles were used in the temperature range of 50-800 C. X-ray powder diffraction analysis was performed on diffractometer Bruker D8 Advance using monochromatic Cu-kα radiation (k = 1.5406 Å). The crystallite size D could be calculated using Scherrer's equation as follows [12,43] :…”

“…[12] The difference in the λ max values of the HL ligand and its complexes can confirm the coordination of the azomethine nitrogen to the metal ions. [43] F I G U R E 2 FT-IR spectra of the ligand (HL) and complexes of Co(II), Ni(II), VO(II), Cr(II), and La(III) at 4000-400 cm À1…”

Molecular Docking, DFT Calculations, Effect of High Energetic Ionizing Radiation, and Biological Evaluation of Some Novel Metal (II) Heteroleptic Complexes Bearing the Thiosemicarbazone Ligand

“…Finally, the optical density was recorded at 560 nm and the subtract background was measured at 620 nm. The optical density should be directly correlated with cell quantity [ 27 , 28 ].…”