Synthesis, Spectroscopic, Antibacterial, Antioxidant, DNA Binding and Cleavage, Molecular Docking Studies of Ni(II) and Cu(II) Complexes of S and N Donor Schiff Base Ligands

Binary metal complexes of the ligands (L), H3FPT and H3FP4MT with Ni(II) and Cu(II) metal ions (M) were synthesized and characterized by different spectral and analytical techniques. Among these complexes, Ni(II)- H3FPT complex was found to be polymeric. The ligands and their complexes inhibited the growth of gram positive and gram negative bacterial strains to a moderate extent. The antioxidant nature of ligands and complexes was also established. Intercalative mode of binding of the complexes with calf thymus (CT) DNA was proposed from electronic absorption titrations, fluorescence quenching studies and viscosity measurements. The complexes showed hydrolytic cleavage of plasmid pBR322. Docking studies of metal complexes with DNA revealed that the complexes of H3FP4MT are more active than H3FPT.

1-Hydroxyanthraquinones Containing Aryl Substituents as Potent and Selective Anticancer Agents

A series of 1,2-, 1,4-disubstituted or 1,2,4-trisubstituted anthraquinone-based compounds was designed, synthesized, characterized and biologically evaluated for anticancer efficacy. 2- or 4-arylated 1-hydroxy-9,10-antraquinones (anthracene-9,10-diones) were prepared by Suzuki–Miyaura cross-coupling reaction of 1-hydroxy-2-bromoanthraquinone, 1-hydroxy-4-iodoanthraquinone or 1-hydroxy-2,4-dibromoanthraquinone with arylboronic acids. The cross-coupling reaction of 2,4-dibromo-9,10-anthraquinone with arylboronic acids provide a convenient approach to 2,4-bis arylated 1-hydroxyanthraquinones with a variety of aryl substituent in the 2 and 4 position. The cytotoxicity of new anthraquinone derivatives was evaluated using the conventional MTT assays. The data revealed that six of the aryl substituted compounds among the entire series 3, 15, 16, 25, 27, 28 were comparable potent with the commercially available reference drug doxorubicin on the human glioblastoma cells SNB-19, prostate cancer DU-145 or breast cancer cells MDA-MB-231 and were relatively safe towards human telomerase (h-TERT)immortalized lung fibroblasts cells. The results suggested that the in vitro antitumor activity of synthesized 2-aryl, 4-aryl- and 2,4-diaryl substituted 1-hydroxyanthraquinones depends on the nature of the substituent within the cyclic backbone. Docking interaction of 2-, 4-substituted and 2,4-disubstituted 1-hydroxyanthraquinones indicates intercalative mode of binding of compounds with DNA topoisomerase. The interaction with the DNA of 4-aryl-13, 15, 16 and 4-(furan-3-yl)-23 1-hydroxyanthraquinones was experimentally confirmed through a change in electroforetic mobility. Further experiments with 1-hydroxy-4-phenyl-anthraquinone 13 demonstrated that the compound induced cell cycle arrest at sub-G1 phase in DU-145 cells in the concentration 1.1 μM, which is probably achieved by inducing apoptosis. 4-Arylsubstituted 1-hydroxyanthraquinones 13 and 16 induced the enhancement of DNA synthesis on SNB19 cell lines.

Amberlite IR-120H Catalyzed Synthesis of 1,3-Diphenylpyrazolechromenoquinolin-6-one Compounds and Their Biological Evaluation

A series of 1,3-diphenylpyrazole-chromenoquinolin-6-one compounds were designed and synthesized by using a greener and recyclable heterogeneous Amberlite IR-120H resin as a catalyst, in the presence of ethanol reflux conditions. Interestingly, the catalyst can be recovered after completion of the reaction and can be reused without loss of catalytic property. Therefore, this method provides a green and environmentally benign much improved protocol for the synthesis of 1,3-diphenylpyrazolechromenoquinolin-6-one compounds. The synthesized library of thirty compounds were tested against their cytotoxicity; moreover, the compounds 5s and 5t exhibited potential cytotoxic activity with IC50 values of 1.22 and 1.64 µM, respectively, on MCF-7 cancer cells. The biophysical studies such as UV-visible, fluorescence and circular dichroism studies indicate that these compounds possess good DNA intercalation ability. In addition, these compounds efficiently inhibit topoisomerase I activity. Molecular docking and viscosity studies support that these compounds exhibited intercalative mode of binding with DNA.

Synthesis, Characterization and DNA Binding Studies of N,N′-bis(2-Hydroxy-5-methylbenzylidene)- 2-hydroxy-propane-1,3-diamine Copper(II) and Nickel(II) Complexes

Two new Schiff base transition metal complexes [Cu(HL)]2.CH3CH2OH (1) and [Ni(HL)] (2) (L = N,N′-bis(2-hydroxy-5-methyl-benzylidene)-2-hydroxy-propane-1,3-diamine) were synthesized and characterized by different physico-chemical and spectroscopic techniques. Structure of complex 1 was determined by single crystal X-ray diffractometer. Both the complexes have distorted square planar geometry. The DNA binding study of two complexes was performed via electronic absorption, cyclic voltammetry, photoluminescence, and viscosity methods and found to be intercalative mode of binding.

DNA Binding Potency and Antimicrobial Analysis of New Indole and Pyrazolone Based Transition Metal(II) Complexes

Some novel series of 5-chloro isatin and 4-aminoantipyrine based Schiff bases with transition metal(II) complexes of (Cu, Co, Ni and Zn) have been prepared and characterized by physical, analytical and spectral data. The synthesized ligand behaves as a neutral tridentate is confirmed by spectral techniques. During the complexation, the stoichiometry ratio 1:2 (metal:ligand) is followed and an octahedral arrangement is adopted by all the metal complexes. The calf-thymus DNA interacts with complexes via an intercalative mode is studied by electronic absorption titration. Moreover, all these synthesized metal(II) complexes were tested against a set of bacterial and fungal strains reveals that complexes exhibit better activity than free ligand.

Synthesis, Structural Characterization, Molecular Modeling and DNA Binding Ability of CoII, NiII, CuII, ZnII, PdII and CdII Complexes of Benzocycloheptenone Thiosemicarbazone Ligand

Background & Objective: Six novel complexes of transition metal namely, [CoLCl2(H2O)2]0.5H2O, [NiLCl2(H2O)2]0.5H2O, [CuLCl2]0.5H2O, [ZnLCl2], [PdLCl2]H2O and [CdLCl2]H2O, where L is benzocycloheptenone thiosemicarbazone ligand, have been obtained. The confirmation of the structures of the obtained metal chelates depends on the different spectral and physicochemical techniques including CHN analysis, infrared spectra, molar conductivity measurement, UV-vis, thermogravimetric analysis and magnetic moment. The infrared spectral results ascertained that the ligand behaved as neutral bidentate connecting the metal centers via N and S atoms of C=N and C=S groups, respectively. Methods: The UV-Vis, molar conductivity and magnetic susceptibility results implied that the geometrical structures of the metal chelates are octahedral for Co(II) & Ni(II) complexes, tetrahedral for Zn(II) & Cd(II) complexes and square planar for Cu(II) & Pd(II) complexes which have been confirmed by molecular modeling studies. Conclusion: Moreover, the mode of interaction between some chosen metal complexes towards SSDNA has been thoughtful by UV-Vis spectra and viscosity measurements. The value of the intrinsic binding constant (Kb) for the examined compounds has been found to be lower than the binding affinity of the classical intercalator ethedium bromide. Also, the viscosity measurements of the complexes proved that they bind to DNA, most likely, by a non-intercalative mode like H-bonding or electrostatic interactions.

Computational Studies of 4-Formylpyridinethiosemicarbazone and Structural and Biological Studies of Its Ni(II) and Cu(II) Complexes

To understand the stability, chelation behaviour, and biological activity of 4-Formylpyridinethiosemicarbazone (H4FPT), it is important to recognize its interactive geometry. Hence, computational studies on geometrically optimized structures of thione and thiol forms of H4FPT were performed. Binary metal complexes of the ligand, H4FPT (L) with the Ni(II) and Cu(II) metal ions (M), were synthesized and characterized by various spectroanalytical techniques as elemental analysis, molar conductance, magnetic susceptibility measurements, LC-MS, TGA, IR, UV-Visible, ESR, and powder XRD. Elemental analysis, LC-MS, and TGA studies indicate 1:2 (ML2) composition for mononuclear Ni(II) complex and 1:1 (ML) composition for dinuclear Cu(II) complex. Electronic absorption titrations, fluorescence quenching studies, and viscosity measurements suggest intercalative mode of binding of the complexes with calf thymus DNA (CT-DNA). These complexes also promote hydrolytic cleavage of plasmid pBR322. The ligand (H4FPT) and its complexes showed moderate-to-good activity against Gram-positive and Gram-negative bacterial strains. The DPPH radical scavenging studies showed antioxidant nature of both complexes.

Synthesis, Structure, DNA Interaction, and SOD Activity of Three Nickel(II) Complexes Containing L-Phenylalanine Schiff Base and 1,10-Phenanthroline

Three hexacoordinated octahedral nickel(II) complexes, [Ni(sal-L-phe)(phen)(CH3OH)]⋅CH3OH (1), [Ni(naph-L-phe)(phen)(CH3OH)] (2), and [Ni(o-van-L-phe)(phen)(CH3OH)]⋅5CH3OH (3) (sal-L-phe = a Schiff base derived from salicylaldehyde and L-phenylalanine, naph-L-phe = a Schiff base derived from 2-hydroxy-1-naphthaldehyde and L-phenylalanine, o-van-L-phe = a Schiff base derived from o-vanillin and L-phenylalanine, and phen = 1,10-phenanthroline), have been synthesized and characterized by elemental analysis, IR spectra, and single-crystal X-ray diffraction. The interactions of these complexes with CT-DNA were studied by UV-Vis absorption spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, and viscosity measurements. The binding constant (Kb) values of 1.82 × 104 M−1 for 1, 1.96 × 104 M−1 for 2, and 2.02 × 104 M−1 for 3 suggest that each of these complexes could bind with DNA in a moderate intercalative mode. Complex 3 exhibited a stronger interaction with CT-DNA than complexes 1 and 2. In addition, the superoxide scavenging activity of these complexes was investigated by the nitrotetrazolium blue chloride (NBT) light reduction method, and the results showed that they exhibited a significant superoxide scavenging activity with the IC50 values of 4.4 × 10−5 M for complex 1, 5.6 × 10−5 M for complex 2, and 3.1 × 10−5 M for complex 3, respectively.

Synthesis and Characterization of Oxidovanadium(IV) Complexes of 2-((E)-(6-Fluorobenzo[d]thiazol-2-ylimino)methyl)-6-methoxyphenol and Their Antimicrobial, Antioxidant, and DNA-Binding Studies

Two novel oxidovanadium(IV) complexes with a new bidentate (O- and N-) imine-based ligand 2-((E)-(6-fluorobenzo[d]thiazol-2-ylimino)methyl)-6-methoxyphenol (HL) were synthesized under in situ experimental condition where VOSO4 acts as a kinetic template in the ratio 2 : 1 (L : M) and mixed ligand complex using 1,10-phenanthroline (phen) in 1 : 1 : 1 (L : M : phen) ratio. The synthesized compounds were structurally characterized by microanalysis, magnetic susceptibility, FTIR, electronic spectra, TG/DTA, ESR, and molar conductance studies. Based on the spectral studies, the complexes have the general composition [VO(L)2] (C1) and [VO(L)phen] (C2) in a square pyramid geometrical fashion. The synthesized compounds were primarily screened for their in vitro growth inhibiting activity against different strains of bacteria, namely, E. coli, B. subtilis, S. aureus, and P. aeruginosa by the disc diffusion method. Also, the antifungal activity was determined against C. albicans and A. niger by the Bateman poisoned technique. The in vitro antioxidant activity of all the compounds was determined by DPPH free radical-scavenging assay. Intercalative mode of DNA-binding properties of the oxidovanadium(IV) complexes with calf-thymus DNA (CT-DNA) was investigated using UV, fluorescence spectra, and viscosity measurements.

Syntheses, crystal structures and DNA-binding activities of divalent Fe, Cu, Zn and Cd complexes with 4′-(furan-2-yl)-2,2′:6′,2″-terpyridine

Five coordination complexes [Fe(ftpy)2](ClO4)2·(H2O)2 (1), [Cu(ftpy)(NO3)(H2O)](NO3) (2), [Cu(ftpy)2]2(ClO4)4·(C2H5OH) (3), [Zn(ftpy)2]·(ClO4)2·(H2O)1.5 (4) and [Cd(ftpy)2]2(ClO4)4·(C2H5OH) (5) (ftpy=4′-(furan-2-yl)-2,2′:6′,2′-terpyridine) have been synthesized and characterized by IR, elemental analysis and single-crystal X-ray diffraction. With the exception of 4, all complexes adopt normal homoleptic [M(ftpy)2]2+ motifs. In the crystal, both hydrogen bonds and face-to-face interactions between furyl and pyridyl rings facilitate the construction of three-dimensional networks. The DNA-binding activities of the five complexes have been investigated by fluorescence emission titration at room temperature suggesting an intercalative mode for 1–3 with a relative order, 3>2>1, and a combined static and dynamic mode for 4 and 5.