ABSTRACT
Novel palladium(II) complexes (7a-7e) of substituted quinoline derivatives were synthesized. The complexes were characterized using various techniques such as thermogravimetric analysis (TGA), elemental analysis, conductance measurement, mass, absorption, infra-red (IR), 1 H NMR, 13 C NMR and energy-dispersive X-ray spectroscopy (EDX). Complexes for herring sperm DNA (HS DNA) binding were explored and absorption titration and the binding constant (Kb ) as well as Gibb's free energy were evaluated. Complex 7d exhibited the highest binding constant, therefore the thermodynamic parameters of 7d at different temperatures were evaluated. To support the results of the absorption titration, fluorescence titration, viscosity measurement and molecular docking studies were performed. The fluorescence quenching data as evaluated from Stern-Volmer equation were used to calculate KSV , Kf and the number of binding sites. The results of all these studies were in good agreement with the absorption study. DNA electrophoretic mobility was performed to explore the possible application of metal complexes as artificial metallonucleases. The antibacterial activity of the complexes was accessed against different pathogenic bacteria and cytotoxicity was measured using brine shrimp and S. pombe.
Subject(s)
Coordination Complexes/chemistry , Coordination Complexes/pharmacology , DNA, B-Form/chemistry , Palladium/chemistry , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Artemia/drug effects , Binding Sites , Coordination Complexes/chemical synthesis , DNA, B-Form/metabolism , Drug Evaluation, Preclinical/methods , Electrophoresis/methods , Electrophoretic Mobility Shift Assay , Ligands , Magnetic Resonance Spectroscopy , Molecular Docking Simulation , Quinolines/chemistry , Schizosaccharomyces/drug effects , Spectrometry, Fluorescence , Spectrometry, X-Ray Emission , ThermodynamicsABSTRACT
Square planar mononuclear platinum(II) complexes having general formula [Pt(Ln)Cl2], (where, Ln = L1-4) were synthesized with neutral bidentate heterocyclic 1,3,5-trisubstituted bipyrazole based ligands. The synthesized compounds were characterized by physicochemical method such as TGA, molar conductance, micro-elemental analysis and magnetic moment, and spectroscopic method such as, FT-IR, UV-vis, 1H NMR, 13C NMR and mass spectrometry. Biological applications of the compounds were carried out using in vitro brine shrimp lethality bioassay, in vitro antimicrobial study against five different pathogens, and cellular level cytotoxicity against Schizosaccharomyces pombe (S. Pombe) cells. Pt(II) complexes were tested for DNA interaction activities using electronic absorption titration, viscosity measurements study, fluorescence quenching technique and molecular docking assay. Binding constants (Kb) of ligands and complexes were observed in the range of 0.23-1.07 × 105 M-1 and 0.51-3.13 × 105 M-1, respectively. Pt(II) complexes (I-IV) display an excellent binding tendency to biomolecule (DNA) and possess comparatively high binding constant (Kb) values than the ligands. The DNA binding study indicate partial intercalative mode of binding in complex-DNA. The gel electrophoresis activity was carried out to examine DNA nuclease property of pUC19 plasmid DNA.
Subject(s)
Anti-Bacterial Agents/pharmacology , DNA/metabolism , Platinum Compounds/chemistry , Platinum Compounds/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Artemia/drug effects , Chemistry Techniques, Synthetic , Cytotoxins/chemistry , Cytotoxins/pharmacology , Deoxyribonucleases/metabolism , Drug Evaluation, Preclinical/methods , Electrophoresis/methods , Magnetic Resonance Spectroscopy , Molecular Docking Simulation , Platinum Compounds/chemical synthesis , Schizosaccharomyces/drug effects , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , ThermogravimetryABSTRACT
Square planar mononuclear platinum(ii) complexes were synthesized in the presence of neutral bidentate heterocyclic (5-quinoline 1,3,5-tri-substituted pyrazole scaffold) ligands and K2PtCl4 salt. The synthesized compounds were characterized by micro-elemental analysis, FT-IR, UV-vis, 1H NMR, 13C NMR, TGA, mass spectrometry and molar conductivity. Their biological activities were investigated by in vitro brine shrimp lethality bioassay, in vitro antimicrobial study against five different pathogens, in vivo cellular level cytotoxicity against Schizosaccharomyces pombe cells, and in vitro anti-proliferation assay. The binding constant Ksv, Kb, Ka values of the complexes were determined by DNA interaction studies. The gel electrophoresis assay was carried out to examine the effect of the complexes on the DNA nuclease of pUC19 plasmid DNA. The docking energies of the ligands (L1-L5 ) and complexes (I-V) were observed in the range of -265.14 to -284.33 kJ mol-1. The synthesized Pt(ii) complexes (I-V) were screened against the MCF-7 (human breast adenocarcinoma) and HCT-116 (human colon carcinoma) cancer cell lines.
ABSTRACT
[This corrects the article DOI: 10.1039/C7MD00472A.].
ABSTRACT
The square planar Pt(II) complexes of the type [Pt(Ln)(Cl2)] (where Ln = L1-3 = thiophene-2-carboxamide derivatives and L4-6 = thiophene-2-carbothioamide derivatives) have been synthesized and characterized by physicochemical and various spectroscopic studies. MIC method was employed to inference the antibacterial potency of complexes in reference to free ligands and metal salt. Characteristic binding constant (Kb) and binding mode of complexes with calf thymus DNA (CT-DNA) were determined using absorption titration (0.76-1.61 × 105 M-1), hydrodynamic chain length assay and fluorescence quenching analysis, deducing the partial intercalative mode of binding. Molecular docking calculation displayed free energy of binding in the range of -260.06 to -219.63 kJmol-1. The nuclease profile of complexes towards pUC19 DNA shows that the complexes cleave DNA more efficiently compared to their respective metal salt. Cytotoxicity profile of the complexes on the brine shrimp shows that all the complex exhibit noteworthy cytotoxic activity with LC50 values ranging from 7.87 to 15.94 µg/mL. The complexes have been evaluated for cell proliferation potential in human colon carcinoma cells (HCT 116) and IC50 value of complexes by MTT assay (IC50 = 125-1000 µg/mL).
Subject(s)
Coordination Complexes/chemistry , DNA/chemistry , Molecular Docking Simulation , Platinum/chemistry , Animals , Artemia/drug effects , Artemia/growth & development , Bacteria/drug effects , Bacteria/growth & development , Cell Proliferation/drug effects , Cell Survival/drug effects , Coordination Complexes/chemical synthesis , Coordination Complexes/pharmacology , DNA/genetics , Drug Design , HCT116 Cells , Humans , Microbial Sensitivity Tests , Thiophenes/chemistryABSTRACT
Palladium(II) complexes of type [Pd(Ln)Cl2] and [Pd(bdt)(Ln)] have been synthesized using 2-acetyl pyridine derivatives(Ln) and benzene-12-dithiol(bdt). The synthesized complexes have been characterized by various analytical techniques like thermo gravimetric analysis, elemental analysis, conductance measurement, and spectroscopic techniques like elemental analysis, mass spectra, absorption spectra, IR, 1H NMR, energy-dispersive X-ray spectroscopy. The interaction of the complexes with calf-thymus DNA (CT-DNA) has been explored by absorption titration, viscosity measurement methods. Based on the observations, an intercalative binding mode of DNA has been proposed. In order to provide additional evidence for the intercalation mode of binding between the complex and CT-DNA, fluorescence titration experiment was performed. In addition, molecular modeling study has been carried out with the aim of establishing the complex's binding mode. Antibacterial activity study of the complexes have been screened against pathogenic bacteria such as Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Serratia marcescens, and Pseudomonas aeruginosa. Gel electrophoresis assay demonstrates that all the complexes can cleave the pUC19 plasmid DNA.
