Syntheses,characterization, in vitro antiglycation and DPPH radical scavenging activities of isatin salicylhydrazidehydrazone and its Mn (II), Co (II), Ni (II), Cu (II), and Zn (II) metal complexes

2-Hydroxy salicylhydrazide isatin hydrazone (L) and its Mn (II), Co (II), Ni (II), Cu (II), and Zn (II), metal complexes were synthesized. ¹H NMR, UV–Vis, IR spectroscopy and elemental (CHN/S) analysis techniques were applied for characterization. TG/DTA techniques revealed that all the synthetic compounds are thermally stable up to 300 °C. They were found non-electrolytes in nature. Furthermore, all these complexes were evaluated for antiglycation and DPPH radical scavenging activities. They showed varying degree of activity with IC₅₀ values between 168.23 and 269.0 μM in antiglycation and 29.63–57.71 μM in DPPH radical scavenging activity. Mn (II), Co (II), Ni (II), Cu (II), and Zn (II), metal complexes showed good antiglycation as well as DPPH radical scavenging activity. The IC₅₀ values for antiglycation activity are 168.23 ± 2.37, 234.27 ± 4.33, 257.1 ± 6.43, 267.7 ± 8.43, 269.0 ± 8.56 Ni for Co, Zn, Mn, Cu, and Ni complexes, respectively, while IC₅₀ value were found to be 29.63 ± 2.76, 31.13 ± 1.41, 35.16 ± 2.45, 43.53 ± 3.12, 57.71 ± 2.61 μM for Cu, Zn, Mn, Co and Ni complexes, respectively, for DPPH radical scavenging activity. These synthesized metal complexes were found to be better active than standards Rutin (IC₅₀ = 294.46 μM) for anti-glycation, and tert-butyl-4-hydroxyanisole (IC₅₀ = 44.7 μM) for DPPH radical scavenging activity.     

Synthesis,spectroscopic characterization,biological screening and in vitro cytotoxic studies of 4‐methyl‐3‐thiosemicarbazone derived Schiff bases and their Co (II), Ni (II), Cu (II) and Zn (II) complexes

A series of twenty compounds inclusive of bidentate Schiff bases derived from condensation of 4‐methyl‐3‐thiosemicarbazide with substituted derivatives of napthaldehyde/benzaldehyde/salicylaldehyde and their mononuclear Co (II), Ni (II), Cu (II) and Zn (II) complexes in molar ratio (1:1) were synthesized and characterized. The coordination behavior, modes of bonding and overall geometry of the compounds was known from the elemental analysis, spectral techniques (IR, UV–Vis, ¹H NMR, ¹³C NMR, ESR and ESI‐mass), magnetic moment measurements, molar conductance, thermal and powder XRD studies. The studies revealed octahedral geometry for all the complexes where ligands coordinated in a neutral bidentate manner (NS) via nitrogen atom of azomethine group and sulphur atom of thione group with the metal centre. In vitro biological effects of the compounds were tested against four bacterial species and two fungal strains. The results indicated that the metal complexes showed a marked enhancement in biocidal activity in comparable with the parent Schiff bases. In vitro anticancer activity against the malignant tumor cell lines; human alveolar adenocarcinoma epithelial cell line (A549), human breast adenocarcinoma cell line (MCF7), human prostate cancer cell line (DU145) and human normal lung cell line (MRC‐5) using MTT assay, exposed compound 16 as a leading member with lowest IC₅₀ value of 10.6 ± 0.14 μM against (A549) cell line.     

Ferrocene conjugated copper(II) complexes of terpyridine and traditional Chinese medicine (TCM) anticancer ligands showing selective toxicity towards cancer cells

Six novel mixed‐ligand copper(II) complexes, namely, [Cu(R‐tpy)(L)]NO₃ ( 1–6 ), where R‐tpy is 4′‐phenyl‐2,2′:6′,2′′‐terpyridine (Ph‐tpy; 1–3 ) and 4′‐ferrocenyl‐2,2′:6′,2′′‐terpyridine (Fc‐tpy; 4–6 ), L is the bidentate O,O donor monoanion of plumbagin (5‐hydroxy‐2‐methyl‐1,4‐naphthoquinone; plum in 1 , 4 ), chrysin (5,7‐dihydroxyflavone; chry in 2 , 5 ) and curcumin (bis(4‐hydroxy‐3‐methoxyphenyl)‐1,6‐diene‐3,5‐dione; curc in 3 , 6 ) have been synthesized and characterized and their in vitro cytotoxicity against cancer cells is evaluated. The energy optimized structures and the frontier orbitals of the complexes have been obtained from the DFT calculations. Complexes 4–6 with a conjugated ferrocenyl moiety and TCM anticancer ligands, namely, plum (in 4 ), chry (in 5 ) and curc (in 6 ) showed potent cytotoxicity giving respective IC₅₀ values of 1.2 μM, 0.62 μM and 0.21 μM in HeLa and 2.0 μM and 1.0 μM and 0.34 μM in MCF‐7 cancer cells while being much less toxic to MCF‐10A normal cells (IC₅₀: 8.3‐17.1 μM). In contrast, complexes 1–3 with a conjugated phenyl moiety were appreciably less toxic to HeLa cells with respective IC₅₀ values of 10.4 μM, 8.1 μM and 5.5 μM when compared with their ferrocenyl analogues 4–6 . Mechanistic studies using Hoechst staining and Annexin‐V‐FITC assays on cancer cells revealed an apoptotic pathway of cell death induced by the complexes. Fluorescence imaging study showed that complex 6 having curcumin as ligand localized primarily in the mitochondria of HeLa cells. Thus, we demonstrate in this study that ferrocene conjugation to copper(II) complexes of TCM anticancer ligands significantly increases the selectivity and cytotoxicity of the resulting complexes towards cancer cells over normal cells.     

Synthesis and biological evaluation of Cu(II), Zn(II), and Ni(II) 3-(4-nitrophenyl)acrylic acid complexes with diamines as potential urease inhibitors

Five new Cu(II), Zn(II), and Ni(II) 3-(4-nitrophenyl)acrylic acid complexes were synthesized and evaluated for inhibitory activity on jack bean urease. All five complexes were structurally determined by single crystal X-ray analysis. Compared with the positive reference acetohydroxamic acid (IC₅₀?=?13.25?μM), Cu(II) complexes 3 and 4 showed the strongest inhibitory activity against jack bean urease (IC₅₀?=?1.23 and 1.17?μM). Ni(II) and Zn(II) complexes also exhibited inhibitory activities (IC₅₀?=?10.09–13.10?μM).     

Synthesis of Substituted Quinolinyl Ether‐based Inhibitors of PI3K as Potential Anticancer Agents

A new strategy for the preparation of 8‐quinolyl ethers 3 ( a – g ), 5 ( a – g ), and 7 ( a – d ) was studied by copper (II)‐catalyzed methodology in the presence of Cs₂CO₃ and acetone–water mixture (1:1). Screening of quinolinyl‐8‐ethers was investigated against anticancer expressive studies to validate new chemical entity in medicinal chemistry. Approaches were evaluated against breast cancer (MCF‐7), skin cancer (G‐361), and colon cancer (HCT 116) cell lines. Inhibitory potentials against phosphoinositide‐3‐kinase (PI3K) enzyme responsible for cancer development have been evaluated by competitive ELISA studies. In PI3K assay, 3a – c were inactive (IC₅₀ > 5 μM), while 3e – g , 5a , 5c – e , 5g , 7a , and 7d showed a moderate activity (IC₅₀ ≥ 0.05 μM). Compounds ( 5b , 5f , 7b , and 7c ) showed significant activity (IC₅₀ < 1.0 μM); thus, their anticancer activities were carried out. Anticancer activity was found to be selective towards breast cancer (MCF‐7); 5b , 5f , 7b , and 7c showed predominant relative percentage activities of 74.12%, 79.04%, 72.56%, and 78.47%, with IC₅₀ values of 5b (2.27 ± 0.88 μM), 5f (1.38 ± 0.60 μM), 7b (2.64 ± 0.86 μM), and 7c (1.87 ± 0.68 μM) compared with the standard doxorubicin 73.14% inhibition (IC₅₀ = 1.98 ± 0.75 μM). Docking study also conducted to find out the binding interactions with p110α (PDB ID: 3T8M) enzyme. Compounds 5b , 5f , 7b , and 7c showed best docking score into the active site of PI3K 12.59, 10.51, 56.52, and 8.61 nM. Structure–activity relationship studies demonstrated that the synthesized compounds are the potential PI3K inhibitors to treat various cancer‐related diseases.     

Synthesis,spectral, structural characterization and biological activity of new palladium(II) complexes containing 3‐acetyl‐8‐methoxy‐2H‐chromen‐2‐one derived Schiff bases

Four different mononuclear palladium(II) complexes of 3‐acetyl‐8‐methoxycoumarin Schiff bases were synthesized and characterized by spectrochemical techniques. Further analysis through X‐ray crystallography confirmed the structures of the complexes. Their interactive ability with Calf Thymus DNA and protein (Bovine Serum Albumin and Human Serum Albumin) were investigated by means of absorption and emission methods. The intercalative mode of binding with DNA was supported by EB displacement studies and viscosity measurements. Configurational changes that occurred in the proteins have been analysed with the help of 3D fluorescence studies. The complexes were shown to have good antimicrobial activity against the tested bacterial and fungal pathogens. In addition, antiproliferative activity of the complexes was evaluated on A549 and MCF‐7 cell lines and the complexes were comparatively more active than the standard drug cisplatin. Among the compounds, complex 3 was the most effective against MCF‐7 (IC₅₀ value of 5.20 ± 0.15 μM) and A549 (5.09 ± 0.13 μM) compared with the other complexes 1 (6.48 ± 0.17 μM; 5.98 ± 0.09 μM), 2 (5.53 ± 0.12 μM; 5.85 ± 0.11 μM), 4 (6.73 ± 0.19 μM; 6.63 ± 0.16 μM) and cisplatin (16.79 ± 0.08 μM; 15.10 ± 0.05 μM) respectively. LDH and NO release assays confirmed the cytotoxic potential of the synthesized complexes.     

Synthesis,characterization, cytotoxicity and computational studies of new phosphine‐ and carbodithioate‐based palladium(II) complexes

In quest of new metallo‐pharmaceuticals with enhanced anticancer activity, four new phosphine‐ and carbodithioate‐based Pd(II) complexes of the type [(R)CS₂Pd(PR₃)Cl] (where R = 4‐(2‐hydroxyethyl)piperazine ( 1 , 2 ), dibenzyl ( 3 , 4 ); PR₃ = diphenyl(p ‐tolyl)phosphine ( 1 , 3 ), tris(4‐tolyl)phosphine ( 2 , 4 )) were synthesized and characterized using elemental analysis, Fourier transform infrared and NMR (¹H, ¹³C and ³¹P) spectroscopies and single‐crystal X‐ray diffraction. The X‐ray diffraction data confirmed the pseudo square‐planar geometry ensuring bidentate coordination mode of carbodithioate ligands. Anticancer activity of the synthesized complexes and their ligands was assessed against human lung (A549), breast (MCF‐7) and prostate (PC3) carcinoma cells using MTT assay. All the tested compounds showed activity in micromolar range. In many cases, the cytotoxicity of the synthesized complexes was higher than or comparable to that of the standard drugs cisplatin and doxorubicin. Complex 3 emerged as the most promising compound with the lowest IC₅₀ values of 4.83, 3.72 and 5.11 μM for A549, MCF‐7 and PC3 carcinoma cell lines, respectively. DNA binding studies were also carried out using UV–visible spectroscopy. We extended our investigations to explore the mechanism of anticancer activity using in silico tools. Based on the mechanism of action of standard drugs used, extensive docking studies were carried out on the three different biomolecular targets.     

Methyl substituent effect on one‐dimensional copper(II) coordination polymers containing biologically active ligands: Synthesis,characterization, DNA interactions and cytotoxicities

Three novel water‐soluble copper(II) complexes – {[Cu(phen)(trp)]ClO₄·3H₂O}_n ( 1 ), {[Cu(4‐mphen)(trp)]ClO₄·3H₂O}_n ( 2 ) and [[Cu(dmphen)(trp)(MeOH)][Cu(dmphen)(trp)(NO₃)]]NO₃ ( 3 ) (phen: 1,10‐phenanthroline; 4‐mphen: 4‐methyl‐1,10‐phenanthroline; dmphen: 4,7‐dimethyl‐1,10‐phenanthroline; trp: l ‐tryptophan) – have been synthesized and characterized using various techniques. Complexes 1 and 2 are isostructural, and exist as one‐dimensional coordination polymers. Complex 3 consists of two discrete copper(II) complexes containing [Cu(trp)(dmphen)(MeOH)]⁺, [Cu(trp)(dmphen)(NO₃)] and one nitrate anion. The binding interaction of the complexes with calf thymus DNA (CT‐DNA) was investigated using thermal denaturation, electronic absorption and emission spectroscopic methods, revealing that the complexes could interact with CT‐DNA via a moderate intercalation mode. The binding activity of the complexes to CT‐DNA follows the order: 3  >  2 > 1 . The pUC19 DNA cleavage activity of the complexes was investigated in the absence and presence of external agents using the agarose gel electrophoresis method. Especially, in the presence of H₂O₂ as an activator, the pUC19 DNA cleavage abilities of the complexes are clearly enhanced at low concentration. Addition of hydroxyl radical scavenger dimethylsulfoxide shows a marked inhibition of the pUC19 DNA cleavage activity of the complexes. In vitro cytotoxic effect of the complexes was examined on human tumor cell lines (Caco‐2, A549 and MCF‐7) and healthy cells (BEAS‐2B). The potent cytotoxic effect of complex 3 , with IC₅₀ values of 1.04, 1.16 and 1.72 μM, respectively, is greater relative to clinically used cisplatin (IC₅₀ = 22.70, 31.1 and 22.2 μM) against the Caco‐2, A549 and MCF‐7 cell lines.     

Anticancer activity of Ophiobolin A,isolated from the endophytic fungus Bipolaris setariae

The present work describes the anticancer activity of Ophiobolin A isolated from the endophytic fungus Bipolaris setariae. Ophiobolin A was isolated using preparative HPLC and its structure was confirmed by HRMS, ¹H NMR, ¹³C NMR, COSY, DEPT, HSQC and HMBC. It inhibited solid and haematological cancer cell proliferation with IC₅₀ of 0.4–4.3 μM. In comparison, IC₅₀ against normal cells was 20.9 μM. It was found to inhibit the phosphorylation of S6 (IC₅₀ = 1.9 ± 0.2 μM), ERK (IC₅₀ = 0.28 ± 0.02 μM) and RB (IC₅₀ = 1.42 ± 0.1 μM), the effector proteins of PI3K/mTOR, Ras/Raf/ERK and CDK/RB pathways, respectively. It induced apoptosis and inhibited cell cycle progression in MDA-MB-231 cancer cells with concomitant inhibition of signalling proteins. Thus, this study reveals that anticancer activity of Ophiobolin A is associated with simultaneous inhibition of multiple oncogenic signalling pathways namely PI3K/mTOR, Ras/Raf/ERK and CDK/RB.     

Synthesis,DNA binding,nuclease activity and cytotoxic studies of a wheel‐shaped octanuclear copper(II) complex based on 1,2,4‐triazole

The antitumor activity shown by many platinum complexes has produced a strong interest in research of new organometallic compounds. Among the metal compounds synthesized and tested, copper compounds have received considerable attention because of their cytotoxic activity against solid tumors. A novel wheel‐shaped octanuclear copper(II) complex with a 1,2,4‐triazole derivative ligand formulated as [Cu₈L₄](ClO₄)₈?11H₂O ( 1 ) (L = 3,5‐bis((bis(2‐hydroxylethyl)amino)methyl)‐4 H‐1,2,4,‐triazole‐4‐amine) has been synthesized and structurally characterized. In 1 , eight Cu atoms are linked through 1,2,4‐triazole units and alkoxide bridges to form a centrosymmetric octanuclear Cu(II) metallomacrocycle. The interaction of complex 1 with calf thymus DNA has been studied using UV absorption, fluorescence and circular dichroism spectroscopies, viscosity measurements and cyclic voltammetry. The apparent binding constant (k_app) value for 1 is 1.59 × 10⁵ M^?1. Furthermore, complex 1 displays efficient oxidative cleavage of supercoiled DNA in the presence of external agents, the rate constant for the conversion of supercoiled to nicked DNA being 2.67 × 10^?5 s^?1. Interestingly, cytotoxicity studies on the MCF‐7 human breast cancer cell line show that the IC₅₀ value of 1 is less than that of cisplatin for the same cell line, revealing that it has the potential to act as an effective metal‐based anticancer drug. Copyright © 2016 John Wiley & Sons, Ltd.     

Synthesis,structural characterization and DNA binding affinity of new bioactive nano‐sized transition metal complexes with sulfathiazole azo dye for therapeutic applications

The azo dye ligand 4‐(5‐chloro‐2‐hydroxyphenylazo)‐N‐thiazol‐2‐ylbenzenesulfonamide (H₂L) formed by the coupling reaction of sulfathiazole and p‐chlorophenol was synthesized and characterized using elemental analysis and Fourier transform infrared (FT‐IR) as well as UV–visible spectra. Nano‐sized divalent Cu, Co, Ni, Mn and Zn complexes of the synthesized azo dye ligand were prepared and investigated using various spectroscopic and analytical techniques. Elemental and thermal analyses indicated the formation of the Cu(II), Ni(II) and Mn(II) complexes in a molar ratio of 1:2 (L:M) while Co(II) and Zn(II) complexes exhibited a 1:1 (M:L) ratio. FT‐IR spectral studies confirmed the coordination of the ligand to the metal ions through the phenolic hydroxyl oxygen, azo nitrogen, sulfonamide oxygen and/or thiazole nitrogen. The geometric arrangements around the central metal ions were investigated applying UV–visible and electron spin resonance spectra, thermogravimetric analysis and molar conductance measurements. X‐ray diffraction patterns revealed crystalline nature of H₂L and amorphous nature of all synthesized complexes. Transmission electron microscopy images confirmed nano‐sized particles and their homogeneous distribution over the complex surface. Antibacterial, antifungal and antitumour activities of the investigated complexes were screened compared with familiar standard drugs to confirm their potential therapeutic applications. The Cu(II) complex showed IC₅₀ of 3.47 μg ml^?1 (5.53 μM) against hepatocellular carcinoma cells, which means that it is a more potent anticancer drug compared with the standard cisplatin (IC₅₀ = 3.67 μg ml^?1 (12.23 μM)). Furthermore, the Co(II), Ni(II), Cu(II) and Zn(II) complexes displayed IC₅₀ greater than that of an applied standard anticancer agent (5‐flurouracil) towards breast carcinoma cells. Hence, these complexes can be considered as promising anticancer drugs. The mode of binding of the complexes with salmon serum DNA was determined through electronic absorption titration and viscosity studies.     

Synthesis, Characterization and the Antioxidative Activity of Copper(II), Zinc(II) and Nickel(II) Complexes with Naringenin

New complexes of Cu^(II), Zn^(II) and Ni^(II) with naringenin have been synthesized and characterized on the basis of elemental analyses, molar conductivities, ¹H-n.m.r., i.r. spectra, u.v. spectra, thermal analyses, and fluorescence spectra. In addition, the suppression ratio for O₂⁻· (a) and OH· (b) of the complexes were studied by spectrophotometric methods. The results show that the effect of the Cu^(II)-complex IC₅₀ (a) = 0.003 μm, IC₅₀ (b) = 0.06 μm is the most remarkable, and the average scavenger ability of the complexes (IC₅₀=0.06–2.67μm) against OH· is higher than that of the ligand (IC₅₀ = 28.5 μm). Taken together, these results indicate that the scavenger effect can be enhanced by the formation of metal-ligand coordination complexes, and the transition-metal ions may have differential and selective roles.     

Half‐sandwich Ruthenium (II) complexes with triphenylamine modified dipyridine skeleton and application in biology/luminescence imaging

Four half‐sandwich ruthenium^II (Ru^II) complexes with triphenylamine‐modifed dipyridine frameworks were synthesized and characterized. The cytotoxicity of target complexes toward A549 (lung cancer cells), HeLa (cervical cancer cells) and HepG2 (hepatoma cells) were obtained by the MTT assay, which were superior to cisplatin with the IC₅₀ values changed from 2.4 ± 0.1 μM to 9.2 ± 2.7 μM. Meanwhile, complexes possess the ability of antimetastasis to cancer cells. Ru^II complexes could be transported by serum albumin, catalyze the conversion of NADH (the reduced state of nicotinamide‐adenine dinucleotide) to NAD⁺ and induce the accumulation of reactive oxygen species, which confirmed the antineoplastic mechanism of oxidation. Ru^II complexes could enter A549 cells followed by a non‐energy dependent cellular uptake mechanism, target lysosomes with the Pearson's colocalization coefficient of 0.75, lead to lysosomal damage, disturb the cell cycle (S phase), and eventually induce apoptosis. The results demonstrate that these Ru^II complexes are potential anticancer agents with dual functions, including metastasis inhibition and lysosomal damage.     

Synthesis,structure, and urease inhibitory activities of Co(III), Mn(II) and Zn(II) complexes with hydrazone derived from protocatechuic acid

[Co^III(L₁)₂·H₂O]NO₃ (1), [Mn^II(L₁)₂·H₂O] (2), and [Zn^II(L₁)₂·H₂O] (3) with a hydrazone derived from protocatechuic acid (HL₁ = C₁₅H₁₃N₃O₃) were designed, synthesized, and characterized by C, H, N elemental analyses, single-crystal X-ray diffraction, and IR spectra, which revealed that the three complexes are similar structures. Docking study has been done. The urease inhibitory activities of the three complexes were tested. Complexes 1 and 3 showed strong inhibitory activity against jack bean urease with IC₅₀ values of 45.9 and 11.64 μM. Complex 2 had no obvious inhibitory activity to urease; the IC₅₀ was > 50 μM.     

Synthesis,Characterization and Anti-oxidative Activity of Cobalt(II), Nickel(II) and Iron(II) Schiff Base Complexes

Six complexes, M(HL)₂ · nH₂O (M=Co, Ni and Fe; n=4) with two ligands, 2-carboxy-benzaldehydebenzoylhydrazone (H₂L¹) and 2-carboxybenzaldehyde-(4′-methoxy)benzoylhydrazone (H₂L²), have been synthesized and characterized on the basis of elemental analyses, molar conductivities, i.r. spectra and thermal analyses. In addition, the suppression ratio for O₂^- (a) and the suppression ratio for OH^· (b) were determined with a 72 spectrophotometer. The 50% inhibition [IC₅₀ (a) and IC₅₀ (b)] of the complexes were studied. This study demonstrated that the complexes have activity in the suppression of O₂^- (a) and OH^· (b). In general, the antioxidative activities increased as the concentration of these complexes increased up to a selected extent. The complexes exhibit more effective antioxidants than the ligands and the series of the ligand (H₂L²) are better than the series of the ligand (H₂L¹) do.     

Coordination Behavior of N‐Donor Schiff Base Derived from 2‐Benzoylpyridine Toward Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Pd(II), and Cr(III) Metal Ions: Synthesis,Spectroscopic and Thermal Studies,and Biological Activity

A new Schiff base was prepared from the reaction of 4,4′‐methylenedianiline with 2‐benzoylpyridine in 1:2 molar ratio, as well as its different metal chelates. The structures of the ligand and its metal complexes were studied by elemental analyses, spectroscopic methods (infrared [IR ], ultraviolet–visible [UV –vis], ¹H nuclear magnetic resonance [NMR ], electron spin resonance [ESR ]), magnetic moment measurements, and thermal studies. The ligand acts as tetradentate moiety in all complexes. Octahedral geometry was suggested for Mn(II ), Cu(II ), Cr(III ), and Zn(II ) chloride complexes and pentacoordinated structure and square planar geometry for Co(II ), Ni(II ), Cu(NO₃ )₂, CuBr₂ , and Pd(II ) complexes. ESR spectra of copper(II ) complexes ( 4 )–( 6 ) at room temperature display rhombic symmetry for complex ( 4 ) and axial type symmetry for complexes ( 5 ) and ( 6 ), indicating ground state for Cu(II ) complexes. The derivative thermogravimetric (DTG ) curves of the ligand and its metal complexes were analyzed by using the rate equation to calculate the thermodynamic and kinetic parameters, which indicated strong binding of the ligand with the metal ion in some complexes. Also, some of these compounds were screened to establish their potential as anticancer agents against the human hepatic cell line Hep‐G₂ . The obtained IC₅₀ value of the copper(II ) bromide complex (4.34 µg/mL ) is the highest among the compounds studied.     

Characterization and thermal studies of nano‐synthesized Mn(II), Co(II), Ni(II) and Cu(II) complexes with adipohydrazone ligand as new promising antimicrobial and antitumor agents

New seven complexes of N₁,N₆‐bis((2‐hydroxynaphthalin‐1‐yl)methinyl))adipohydrazone (H₂L) with MnCl₂•4H₂O, CoCl₂•6H₂O, NiCl₂•6H₂O, CuCl₂•2H₂O, Cu(NO₃)₂•3H₂O, CuSO₄•5H₂O, and Cu(OAc)₂•2H₂O have been prepared and characterized by the aid of elemental and thermal analyses, spectra (FT‐IR, ¹H NMR, MS, UV‐Vis, ESR, X‐ray powder diffraction), molar conductance and magnetic moment measurements. The XRD results unambiguously confirmed the nano‐sized particles of the complexes. The results showed that H₂L behaves as dibasic tetra‐dentate ligand towards the metal ions of interest. The low molar conductance values revealed the non‐electrolytic nature for the chelates. The magnetic moment data, UV‐Vis and ESR spectra denoted the formation of octahedral geometries for Mn(II) and Ni(II) complexes, whereas Co(II), Cu(II) complexes exhibited tetrahedral arrangement. The activation parameters for the thermal decomposition stages were calculated from TGA curves using Coats‐Redfern and Horowitz–Metzger methods. The obtained data were confirmed by 3‐D molecular modeling of the ligand and some complexes. The investigated compounds were screened for their antimicrobial activities against different types of organisms and antitumor activities towards human liver Carcinoma (HEPG2) cell to access their potential chemotherapeutic use. The free ligand (H₂L) exhibited a weak inhibition of cell viability with IC₅₀ of 11.80 μg/ml, complexes 4 , 6 and 7 showed a moderate activity with IC₅₀ of 5.56, 7.71 and 5.67 μg/ml, whereas complexes 1 , 2 , 3 , and 5 displayed a strong anticancer activity with IC₅₀ of 4.65, 3.97, 3.30 and 4.84 μg/ml, compared with IC₅₀ value of 4.73 μg/ml for the doxorubicin (standard cytotoxin drug).     

Crystal structures and in vitro anticancer studies on new unsymmetrical copper(II) Schiff base complexes derived from meso-1,2-diphenyl-1,2-ethylenediamine: a comparison with related symmetrical ones

Two new unsymmetrical copper(II) Schiff base complexes, [CuLⁿ(py)]ClO₄ (n = 1, 2) in which Lⁿ represents a tridentate N₂O type Schiff base ligand, were synthesized. Lⁿs were derived from monocondensation of meso-1,2-diphenyl-1,2-ethylenediamine with salicylaldehyde or 3-methoxysalicylaldehyde. The reaction between [CuLⁿ(py)]ClO₄ and other salicylaldehyde derivatives resulted in new N₂O₂ unsymmetrical tetradentate Cu^II complexes, CuL^3–6. Crystal structures of [CuL¹(py)]ClO₄, CuL⁴, and CuL⁵ were obtained. These new complexes as well as a series of related symmetrical ones (i.e. CuL^7–12) were tested for their in vitro anticancer activity against human liver cancer cell line (Hep-G2) by MTT and apoptosis assay. All of the complexes showed considerable cytotoxic activity against tumor cell lines (IC₅₀ = 5.13–16.24 μg mL^?1). The symmetrical CuL⁷ was the most potent anticancer derivative (IC₅₀ = 5.13 μg mL^?1) compared to the control drug 5-FU (IC₅₀ = 5.4 μg mL^-1, p < 0.05). Flow cytometry experiments showed that the copper derivatives especially [CuL²(py)]ClO₄ and CuL⁷ induced more apoptosis on Hep-G2 tumor cell lines compared to 5-FU.     

Synthesis,characterization and anticancer studies of bis-(N-methyl-1-phenyldithiocarbamato) Cu(II), Zn(II), and Pt(II) complexes: single crystal X-ray structure of the copper complex

Abstract

Cu(II), Pt(II), and Zn(II) complexes of N-methyl-1-phenyldithiocarbamate were synthesized and characterized by FTIR, NMR, UV-visible spectroscopy and elemental analysis. The complexes were formulated as [Cu(L)₂], [Zn(L)₂] and [Pt(L)₂] (where L?=?N-methyl-1-phenyldithio­carbamate) in which two molecules of the ligands coordinate to the metal ions in a bidentate chelating fashion. This is confirmed by elemental analysis and the presence of strong single bands at 952, 951, and 955?cm^?1 for Cu(II), Pt(II), and Zn(II) complexes, respectively, in the FTIR spectra. The electronic spectra of Pt(II) and Cu(II) complexes are consistent with four-coordinate square planar geometry. Single crystal X-ray of [Cu(N-mpDTC)₂] confirmed square planar structural arrangement (CuS₄) in which the ligands are asymmetrically bonded to the Cu(II) ion building a centrosymmetric monomer entity. The S-Cu-S bite angle is 77.95° (3) whereas the intramolecular N–C bond length is 1.318 Å and trans S1¹-Cu-S1?=?S2¹-Cu-S2 is 180°, which are consistent with reported copper thiolates in square planar environment. In vitro antiproliferative activity of the complexes against three human cancer cell lines showed that the zinc complex has better activity compared to Cu and Pt complexes, with IC₅₀ values of 14.28, 22.74 and 20.10?μM against TK10, UACC62, and MC7 cell lines, respectively.     

Unusual coordination mode of aroyl/acyl thiourea ligands and their π‐arene ruthenium (II) piano‐stool complexes: Synthesis,molecular geometry,theoretical studies and biological applications

Two mononuclear ruthenium complexes ( 1 and 2 ) with aroyl/acylthiourea as an ancillary ligand of type, [(η⁶‐p‐cymene)RuCl(L‐N,S)], where [ L1  = 2,4‐dichloro‐N‐(o‐tolylcarbamothioyl)benzamide] and L2  = N‐(phenylcarbamothioyl)cyclohexanecarboxamide] were synthesized and well characterized. The single crystal X‐ray diffraction studies revealed the coordination mode and the geometry of the complexes. The two complexes adopted general piano‐stool (three‐legged) geometry with a novel coordination mode of aroyl/acylthiourea through amide N (anionic) and thiocarbonyl S (neutral). This type of monobasic bidentate coordination of the aroyl/acylthiourea ligand was witnessed the first time around the metal ion. The coordination of the complexes was well explained through geometric parameters and frontier molecular orbital parameter values computed at the B3LYP/SDD level. The synthesized complexes were also screened for their antibacterial, antifungal, antioxidant and in vitro antiproliferative activities. Complexes exhibited good antimicrobial agents against various pathogens. The antioxidant activity of the complex 2 has shown most potent activity with IC₅₀ value of 48.55 ± 1.7 μM compared to the reference drug. In addition, the in vitro antiproliferative activity of the complex 2 showed excellent activity against HepG‐2 cell line with the IC₅₀ value of 24.30 ± 1.20 μM which is close to Doxorubicin standard drug.