DNA interaction, anticancer, cytotoxicity and genotoxicity studies with potential pyrazine-bipyrazole dinuclear µ-oxo bridged Au(III) complexes.

Pyrazine-bipyrazole-based µ-oxo bridged dinuclear Au(III) complexes were synthesized and characterized by various spectrometric (1H-NMR, 13C (APT) NMR, FT-IR, Mass spectrometry) and analytical techniques (elemental analysis and conductance measurement). The evaluation of DNA binding activity by UV-Vis absorption spectra and viscosity measurement demonstrated that all the compounds intercalate in between the stacks of DNA base pair and the binding constant values were observed in the range of 5.4 × 104-2.17 × 105 M-1. The molecular docking study also supports the intercalation mode of binding. The anti-proliferation activity of complexes on A549 (Lung adenocarcinoma) cells by MTT assay demonstrated IC50 values in the range of 47.46 -298.12 µg/mL. The genotoxicity of compounds was checked by smearing observed in the DNA of S. pombe cell under the influence of complexes. The in vivo cytotoxicity of compounds against brine shrimp demonstrated the LC50 values in the range of 4.59-27.22 µg/mL. The promising results of the Au(III) complexes received significant attention and make them suitable for the new metallodrugs after the detailed mechanistic biological study.

Synthesis, characterization, and biological applications of pyrazole moiety bearing osmium(IV) complexes.

Osmium (IV) complexes with pyrazole nucleus containing ligands were synthesized. Os(IV) compounds were characterized using ESI-MS, ICP-OES, IR spectroscopy, electronic spectroscopy, conductance, and magnetic measurements. Whereas, ligands were characterized by heteronuclear spectroscopy, (1H and 13C), IR spectroscopy, and elemental analysis. All the compounds were tested for their potential to interact with HS-DNA by absorption titration, fluorescence spectroscopy, viscosity measurement, and docking study. The quenching constant and Stern Volmer constant values were calculated using fluorescence study. The synthesized compounds were studied for in-vitro bacteriostatic and cytotoxic activities. The cancer cell line studies of all the synthesized complexes were carried out on human lung cancer cells (A549).Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.1921795 .

Fluorescence, DNA Interaction and Cytotoxicity Studies of 4,5-Dihydro-1H-Pyrazol-1-Yl Moiety Based Os(IV) Compounds: Synthesis, Characterization and Biological Evaluation.

Osmium(IV) pyrazole compounds and ligands were synthesized and well characterised. Ligands were characterized by heteronuclear NMR spectroscopy (1H & 13C), elemental analysis, IR spectroscopy and liquid crystal mass spectroscopy. Os(IV) complexes were characterized by ESI-MS, ICP-OES, IR spectroscopy, conductance measurements, magnetic measurements and electronic spectroscopy. Binding of compounds with HS-DNA were evaluated using viscosity measurements, absorption titration, fluorescence quenching, and molecular docking, which show effective intercalation mode exhibited by compounds. Binding constant of Os(IV) complexes are found to be 8.1 to 9.2 × 104 M-1. Bacteriostatic and cytotoxic activities were carried out to evaluate MIC, LC50, and IC50. The compounds have been undergone bacteriostatic screening using three sets of Gram+ve and two sets of Gram-ve bacteria. MIC of complexes are found to be 72.5-100 µM, whereas that of ligands fall at about 122.5-150 µM.. LC50 count of ligands fall in the range of 16.22-17.28 µg/mL whereas that of complexes of Os(IV) fall in the range of 4.87-5.87 µg/mL. IC50 of osmium compounds were evaluated using HCT-116 cell line. All the Os(IV) compounds show moderate IC50.

DNA interaction, in vivo and in vitro cytotoxicity, reactive oxygen species, lipid peroxidation of -N, S donor Re(I) metal complexes.

N, S donor ligands (L1-L5){L1-L5 = 1,5-bis(4-chlorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L1), 1-(4-bromophenyl)-5-(4-chlorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L2), 5-(4-chlorophenyl)-3-(thiophen-2-yl)-1-(p-tolyl)-4,5-dihydro-1H-pyrazole (L3), 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L4), 5-(4-chlorophenyl)-1-(4-nitrophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L5)} were synthesized by Claisen-Schmidt condensation and characterized by spectrometric methods. The complexes (I-V) were synthesized by ligand combination followed by metal chelation. The binding of the rhenium complexes to Herrin sperm DNA was monitored by UV spectroscopy and viscosity measurements. The groove binding was suggested as the most possible mode, and the Kb values of the complexes were calculated. The mode of interaction was furthermore confirmed by molecular docking. Brine shrimp lethality and Saccharomyces cerevisiae cytotoxicity against the eukaryotic and prokaryotic cells showed the toxic nature of the synthesized compounds. All compounds were found active against S. cerevisiae, which was confirmed by increased ROS production, and DNA damage as compared to untreated yeast cell culture. The oxidative harm to cell structures was affirmed by lipid peroxidation. An antimicrobial study was carried out by estimating minimum inhibitory concentration against two Gram-positive and three Gram-negative bacteria. All complexes show good antiproliferative activity against the HCT 116 cell line. All synthesized complexes are biologically more active than the corresponding ligands.

Tetrazolo[1,5-a]quinoline moiety-based Os(IV) complexes: DNA binding/cleavage, bacteriostatic and photocytotoxicity assay.

Biological applications of platinum group metal-based complexes have been widely explored in synthetic and inorganic chemistry. The compounds have been subjected to DNA binding, DNA cleavage, In-vivo and In-vitro photocytotoxicity (HCT-116 cell line) and bacteriostatic activities. Binding constant of complexes are 1.42-5.62 × 104 M-1, whereas that of ligands are 1.12-4.72 × 104 M-1. Ksv of complexes are about 1.32-5.21 × 103 M-1, whereas Kf is about 1.24-6.83 × 103 M-1. IC50 of compounds screened using HCT-116 cell line in dark are found to be 121-342 µg/mL. Whereas photocytotoxicity is found in the range of 48-316 µg/mL. Docking energy of molecules have been evaluated to evaluate efficacy of binding. Molecular docking energy of complexes are in the range of -286.00 to -303.11 kJ/mol. Whereas that of ligands are -254.03 to -282.96 kJ/mol. MIC of complexes are 47 ± 2.5 to 77.50 ± 7.5 µM. LC50 values of ligands fall in the range of 4.05-19.72 µg/mL and that of Os(IV) complexes fall in the range of 3.99-15.99 µg/mL. The Os(IV) complexes dominate in proving its potentiality compared to N, N-donor ligands in biological activities. [Formula: see text]Communicated by Ramaswamy H. Sarma.

Biological activities of pyrazoline-indole based Re(I) carbonyls: DNA interaction, antibacterial, anticancer, ROS production, lipid peroxidation, in vivo and in vitro cytotoxicity studies.

Hetero mononuclear rhenium(I) metal complexes (I-V) using different substituted indole-pyrazoline based ligands were synthesized and characterized by spectroscopic and analytical methods. The binding of the rhenium complexes to Herring sperm DNA was monitored by UV spectroscopy, viscosity measurements, and molecular docking studies; groove binding was suggested as the most possible mode and the DNA-binding constants of the complexes were evaluated. In vivo and in vitro cytotoxicity of compounds were evaluated against the brine shrimp and S. cerevisiae cells. An antimicrobial study was carried out by estimating MIC (Minimum Inhibitory Concentration) against two Gram-positive and three Gram-negative bacteria. All synthesized complexes are biologically more active than the corresponding ligands. The anti-proliferation activity of complexes was evaluated on MCF-7, HCT116, and A549 cancer cells by MTT assay. The toxicity profile of synthesized compounds was confirmed by H2O2 production by reactive oxygen species. The increased concentration of lipid peroxidation end products increased free radicals, which enhancing the oxidative stress level in living organisms and results in cell death.

Synthesis, Characterization and Biological Application of Pyrazolo[1,5-a]pyrimidine Based Organometallic Re(I) Complexes.

The neutral rhenium(I) complexes (I-VI) of type [ReCl(CO)3Ln-] where L1 = 7-phenyl-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L2 = 7-(4-bromophenyl)-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimi- dine, L3 = 7-(4-chlorophenyl)-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L4 = 7-(2-chlorophenyl) -5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L5 = 7-(4-methoxyphenyl)-5-(pyridin-2-yl)pyrazolo [1,5-a]pyrimidine, L6 = 5-(pyridin-2-yl)-7-(p-tolyl)pyrazolo[1,5-a]pyrimidine were synthesized and characterized by 13C-APT, 1H-NMR, IR, electronic spectra, magnetic moment and conductance measurement. The anti-proliferative activity on HCT116 cells by MTT assay suggests potent cytotoxic nature of complexes, even some complexes have better activity than standard drug cisplatin, oxaliplatin, and carboplatin. The complexes found to have better antimicrobial activity compare to pyrazolo pyrimidine ligands. The theoretical study of compounds-DNA interactions was examined by molecular docking as a supportive tool to the experimental data, which suggests the groove mode of binding. The values of docking energy for compounds-DNA interaction were found in the range of -230.31 to -288.34 kJ/mol. The intrinsic binding constant values of complexes (1.1-3.5×105 M-1) were found higher than the ligands (0.32-1.8×105 M-1).

Synthesis, characterization and biological activities of imidazo[1,2-a]pyridine based gold(III) metal complexes.

Five imidazo [1,2-a]pyridine derivatives and their Au(III) complexes were synthesized. The compounds were characterized by 1H-NMR, 13C-NMR, IR, mass, UV-visible, elemental analysis, conductivity and magnetic measurement studies. All the compounds were screened for diverse biological activities to check the effect of coordination of Au(III) with imidazo [1,2-a]pyridine heterocycles. The DNA interaction ability of compounds were studied as the change in absorption maxima and position of HS-DNA in presence of compounds and viscosity measurement due to change in DNA length under the influence of compounds. The computational insight of compound-DNA interaction was taken in docking study. All the results suggest intercalation mode of binding. The cellular level cytotoxic nature of compounds was evaluated using trypan blue dye staining of dead cell in cell viability assay. The smearing of DNA was observed, while DNA extracted from S. pombe cells in presence of complexes was subjected to gel electrophoresis, which shows their toxic effect on DNA. The complexes were evaluated for cytotoxicity on human A549 (Lung adenocarcinoma) cell line by MTT assay (IC50 values). The in vitro cytotoxicity in terms of LC50 value was checked on a simple zoological organism, brine shrimp.

Fluorescence and absorption studies of DNA-Pd(II) complex interaction: Synthesis, spectroanalytical investigations and biological activities.

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.

Half Sandwich Rhodium(III) and Iridium(III) Complexes as Cytotoxic and Metallonuclease Agents.

Half sandwich complexes of the type [(η5-C5Me5)M(L1-3)Cl]Cl.2H2O were synthesized using [{(η5-C5Me5)M(µ-Cl)Cl}2], where M = Rh(III)/Ir(III) and L1-3 = pyrimidine-based ligands. The complexes were characterized by spectral analysis. DNA interaction studies by absorption titration and hydrodynamic measurement and suggest intercalative mode of binding of complexes with CT-DNA. The molecular docking study also supports intercalation of the complexes between the stacks of nucleotide base pairs. The gel electrophoresis assay demonstrated the ability of the complexes to interact and cleave plasmid DNA. Minimum inhibitory concentrations (MIC) of the complexes were investigated by the microdilution broth method. The cytotoxic properties of the metal complexes were evaluated using brine shrimp lethality bioassay.

DNA Interaction, in vitro Antibacterial and Cytotoxic Activities of Ru(III) Heterochelates.

Ruthenium(III) complexes [Ru(bphtpy)(PPh3)Cl3] (bphfpy = diphenylfuranylpyridine derivatives) were synthesized and characterized by LCMS, IR spectroscopy, elemental analysis and magnetic measurements. All the complexes were screened for their antibacterial activity in terms of minimum inhibitory concentration against two Gram-positive and three Gram-negative bacterial species. DNA binding study by absorption titration and viscosity measurement shows that complexes bind in an intercalating mode, which is also confirmed by molecular docking. All the complexes were also screened for the DNA nuclease property of pUC19 plasmid DNA. The cytotoxicity study of the synthesized complexes was performed to elucidate the LC50 values to find out the toxicity profile of the complexes.

Evolution of 1, 3, 5-trisubstituted bipyrazole scaffold based platinum(II) complexes as a biological active agent.

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.

Synthesis, characterization and biological application of 5-quinoline 1,3,5-trisubstituted pyrazole based platinum(ii) complexes.

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.

Correction: Synthesis, characterization and biological application of 5-quinoline 1,3,5-trisubstituted pyrazole based platinum(ii) complexes.

[This corrects the article DOI: 10.1039/C7MD00472A.].

Biological Significance of Hetero-Scaffolds Based Gold(III) Complexes.

Synthesized ligands and complexes, [Au(Ln)Cl2]Cl, have been characterized by various techniques such as elemental analysis, LC-MS, FT-IR, UV-Vis, 1H and 13C NMR spectroscopy, conductance measurement and magnetic moments measurement. The experimental results show that complexes exhibit higher antibacterial activity against Gram(+ve) and Gram(-ve) microorganisms than free ligands. The in vitro cytotoxicity and cellular level cytotoxicity suggest that Au(III) complexes show better activity than corresponding ligands. The DNA interaction study has been evaluated using absorption titration. The experimental evidence indicates (Kb = 1.08-3.44 • 105 M-1) that all the complexes have been bind to HS-DNA by intercalation mode. To further verify the nature of interaction viscosity measurement and molecular modeling have been carried out which suggest the intercalation binding between complex and DNA. The Schizosaccharomyces pombe cell DNA cleavage has been performed using agarose gel and their photographic images of complexes show smearing of DNA due to DNA cleavage from the nucleus.

Design, synthesis, MTT assay, DNA interaction studies of platinum(II) complexes.

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).

Acetyl pyridine-based palladium(II) compounds as an artificial metallonucleases.

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.

Copper(II) Complexes with N,O-Donor Ligands and Ofloxacin Drug as Antibacterial, DNA Interacting, Cytotoxic and SOD Mimic Agent.

ABSTRACT: The N,O-donor bidentate ligands (L (1) -L (7) ) derived from the reaction between chalcones and pyridinium salt of 2-acetyl furan were synthesized and characterized by IR and NMR spectroscopic techniques. Their complexes [1-7] of Cu(II) were synthesized and characterized by elemental analysis, magnetic measurements, TG analyses, IR and mass spectroscopy. Synthesized complexes were carried out for their biological elucidation using different biological experiments like minimum inhibitory concentration, DNA binding and cleavage study, cytotoxicity, and antiradical activity. Efficient cleavage of pUC19 DNA was observed for all the test complexes than the reference drug. GRAPHICAL ABSTRACT: Increase in DNA chain length and hence the relative viscosity as the complexes binds to DNA via intercalative mode and involves a strong stacking interaction between an aromatic chromophore and the DNA base pair.

Antimalarial, antimicrobial, cytotoxic, DNA interaction and SOD like activities of tetrahedral copper(II) complexes.

The mononuclear copper(II) complexes with P, O-donor ligand and different fluoroquinolones have been synthesized and characterized by elemental analysis, electronic spectra, TGA, EPR, FT-IR and LC-MS spectroscopy. An antimicrobial efficiency of the complexes has been tested against five different microorganisms in terms of minimum inhibitory concentration (MIC) and displays very good antimicrobial activity. The binding strength and binding mode of the complexes with Herring Sperm DNA (HS DNA) have been investigated by absorption titration and viscosity measurement studies. The studies suggest the classical intercalative mode of DNA binding. Gel electrophoresis assay determines the ability of the complexes to cleave the supercoiled form of pUC19 DNA. Synthesized complexes have been tested for their SOD mimic activity using nonenzymatic NBT/NADH/PMS system and found to have good antioxidant activity. All the complexes show good cytotoxic and in vitro antimalarial activities.