RUE Values Research Articles

Design, synthesis and anticancer evaluation of novel half-sandwich Ru(II) complexes bearing pyrazalone moiety: Apoptosis inducers based on mitochondrial dysfunction and G0/G1 arrest

Six half-sandwich Ru(II) complexes (Ru1-Ru6), integrated with 5-phenyl-2-(pyridin-2-yl)-2,4-dihydro-3H-pyrazol-3-one (PDPO1-PDPO6) ligands, were synthesized and spectroscopically characterized. The structure of Ru3 that crystallized as a monoclinic crystal with P21/c space group was further confirmed by X-ray single crystal diffraction. Prototropic tautomerism within the complexes transformed OH-form ligands to NH-form, forming a hydrogen bond (Cl1---H-N3). The complexes and ligands' cytotoxicity was assessed against several cancerous (HepG2, A549, MCF-7) and normal Vero cell lines. Relative to the ligands and Cisplatin, complexes (Ru2, Ru3, Ru5, Ru6) exhibited potent cytotoxicity against cancer cells, with IC50 values from 2.05 to 15.69 μM/L, excluding Ru1 and Ru4. Specifically, Ru2, Ru3, and Ru5 demonstrated superior anti-HepG2 properties. Compared to Cisplatin, Ru2 and Ru5 were less toxic to Vero cells, highlighting their enhanced selectivity in toxicity. Structure-activity relationship (SAR) studies indicated that t-butyl substitution (in Ru2) or -Cl (in Ru5) on the benzene ring significantly improved the selective toxicity. These complexes manifested substantial lipophilicity, cellular uptake, and were quickly hydrolyzed to Ru-H2O species. Roughly positive correlations were observed between hydrolysis rate, lipophilicity, cellular uptake, and anticancer activities. Ru2, investigated specifically, induced apoptosis in HepG2 cells at concentrations of 10 and 20 μM/L through ROS-mediated mitochondrial dysfunction and G0/G1phase arrest, associated with altered P21, cyclin D, and CDK4 expression levels.

Synthesis and photobiological evaluation of Ru(II) complexes with expanded chelate polypyridyl ligands

Photoreactive Ru(II) complexes capable of ejecting ligands have been used extensively for photocaging applications and for the creation of “photocisplatin” reagents. The incorporation of distortion into the structure of the coordination complex lowers the energy of dissociative excited states, increasing the yield of the photosubstitution reaction. While steric clash between ligands induced by adding substituents at the coordinating face of the ligand has been extensively utilized, a lesser known, more subtle approach is to distort the coordination sphere by altering the chelate ring size. Here a systematic study was performed to alter metal-ligand bond lengths, angles, and to cause intraligand distortion by introducing a “linker” atom or group between two pyridine rings. The synthesis, photochemistry, and photobiology of five Ru(II) complexes containing CH2, NH, O, and S-linked dipyridine ligands was investigated. All systems where stable in the dark, and three of the five were photochemically active in buffer. While a clear periodic trend was not observed, this study lays the foundation for the creation of photoactive systems utilizing an alternative type of distortion to facilitate photosubstitution reactions.

Synthesis and Photobiology Evaluation of Ru(Ii) Complexes with Expanded Chelate Polypyridyl Ligands

Synthesis and Photobiology Evaluation of Ru(Ii) Complexes with Expanded Chelate Polypyridyl Ligands

Cytotoxicity evaluation and DNA interaction of RuII-bipy complexes containing coumarin-based ligands.

Although there are various treatment options for cancer, this disease still has caused an increasing number of deaths, demanding more efficient, selective and less harmful drugs. Several classes of ruthenium compounds have been investigated as metallodrugs for cancer, mainly after the entry of imidazolH [trans-RuCl4-(DMSO-S)(imidazole)] (NAMI-A) and indazolH [trans-RuCl4-(Indazol)2] (KP1019) in clinical trials. In this sense, RuII complexes with general formula [Ru(L1-3)(bipy)2]PF6 (1-3) (L1 = ethyl 3-(6-methyl-2-oxo-2H-chromen-3-yl)-3-oxopropanoate, L2 = ethyl 3-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-3-oxopropanoate, L3 = ethyl 3-(8-methoxy-2-oxo-2H-chromen-3-yl)-3-oxopropanoate and bipy = bipyridine) have been synthesized. The crystal structure of 2 revealed that the RuII atom lies on a distorted octahedral geometry with the deprotonated ligand (L2-) coordinated through β-ketoester group oxygen atoms. In vitro cytotoxic activity of the compounds was evaluated against 4T1 (murine mammary carcinoma) and B16-F10 (murine metastatic melanoma) tumor cells, and the non-tumor cell line BHK-21 (baby hamster kidney). Coordination with RuII resulted in expressive enhancement of cytotoxic activity. The precursors were inactive below 100 μM and the final RuII complexes (1-3) showed IC50 ranging from 2.0 to 12.8 μM; 2 being the most potent compound. DNA interaction studies revealed a greater capacity of the complexes to interact with DNA than the ligands, where, 2 exhibited the highest Kb constant of 2.2 × 104 M-1. Fluorescence investigation demonstrated that 1-3 are capable of quenching the fluorescence emission of the EtdBr-DNA complex up to 40%. Molecular docking showed that the interaction of 1-3 between the DNA base pairs from the coumarin portion was with scores of 67.28, 68.62 and 64.88, respectively, and 75.45 for ellipticine, suggesting an intercalative mode of binding. Our findings show that the RuII complexes are eligible for continuing to be investigated as potential antitumor compounds.

Synthesis, characterization and biological evaluation of novel octahedral Ru(III) complexes containing pentadentate Schiff base ligands

Synthesis, characterization and biological evaluation of novel octahedral Ru(III) complexes containing pentadentate Schiff base ligands

In vitro and in vivo evaluation of first-generation carbosilane arene Ru(II)-metallodendrimers in advanced prostate cancer

BackgroundProstate cancer is the fifth cause of death among men worldwide. Patients suffering resistant prostate tumor, unresponsive to common treatments, can only be treated with palliative therapy. Materials and methodsRuthenium(II) carbosilane metallodendrimers containing arene moieties were evaluated as a novel antitumor nanotherapy against resistant prostate cancer. The preclinical evaluation included relevant in vitro, ex vivo and in vivo assays, in an experimental mice model of human prostate cancer. ResultsPromising cytotoxic, antiproliferative and antimetastatic behaviors were observed. After treatment with these nanocompounds, mice underwent a significant reduction of tumor volume, in comparison to non-treated animals. ConclusionsThe selective antitumor behavior and the lack of toxicity, potentially make ruthenium(II) metallodendrimers promising agents for cancer therapy.

Biological and catalytic evaluation of Ru(II)‐p‐cymene complexes of Schiff base ligands: Impact of ligand appended moiety on photo‐induced DNA and protein cleavage, cytotoxicity and C‐H activation

Two organometallic Ru(II)‐p‐cymene complexes of the type [Ru(η6‐p‐cymene)(L)Cl]PF6 1 and 2, where L is N,N‐bis(4‐isopropylbenzylidene)ethane‐1,2‐diamine (bien, L1) or N,N‐bis (pyren‐2‐ylmethylene)ethane‐1,2‐diamine (bpen, L2) have been prepared and characterized well. Because of appended pyrenyl groups in coordinated bpen ligand, the complex 2 exhibits higher DNA and protein binding than complex 1 in which isopropylbenzyl groups are incorporated. Interestingly, the luminescent characteristic complex 2 is unique in displaying DNA cleavage after light activation by UVA light at 365 nm through oxygen dependent mechanism. AFM analysis attests the photo‐induced DNA fragmentation ability of complex 2. Also, the complex 2 cleaves the protein after light exposure in a non‐specific manner suggesting that it can act as a protein photo cleaving agent. In contrast to the trend of DNA and protein interaction of complexes, the complex 1 exhibits cytotoxic activity against human breast carcinoma (MCF‐7) and liver carcinoma (HepG2) with potency higher than that of complex 2 due to enhanced hydrophobicity of isopropyl groups present in p‐cymene and bien ligands. Indeed, complex 2 is inactive against MCF‐7 and HepG2 cancer cell lines even up to 200 μM concentration. The AO/EB staining assay reveals that the complex 1 is able to induce late apoptotic mode of cell death in breast cancer cells, which is further confirmed by inter‐nucleosomal DNA cleavage. Furthermore, the complexes 1 and 2 are evaluated for their catalytic activities and found to be working well for the β‐carboline directed C–H arylation to afford the desired products in good yield (40–47%).

Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands

New water soluble, enantiopure arene ruthenium compound SRuSN-(1R,4S)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (Bn = benzyl, 1a′) has been synthesized. The novel compound along with that previously described RRuRN-(1S,4R)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (1a) was evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of novel ruthenium derivative 1a′ was determined by single crystal X-ray crystallography. Both enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3, lung A-549, pancreas MIA PaCa-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. Both enantiomers are active and versatile cytotoxic agents, showing IC50 values from 2 to 12 times lower than those found for cisplatin in the different cell lines evaluated. The mechanism of cell death induced by the metal compounds was analyzed in A-549 and Jurkat cell lines. Derivatives 1a and 1a′ induced apoptotic cell death of A-549 cells while dose-dependent cell death mechanisms have been found in the Jurkat cell line. Compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, revealing moderate binding affinity of 1a and 1a′ towards duplex DNA. Finally, the efficacy of 1a in a preliminary in vivo assay of PC-3 xenografts in nude mice has been evaluated, resulting in a promising inhibition of tumor growth by 45%. Analysis of tumor tissue also showed a significant decrease of levels of crucial molecules in the invasive phenotype of PC-3 cells.

Synthesis and Biological Evaluation of Ru(II) and Pt(II) Complexes Bearing Carboxyl Groups as Potential Anticancer Targeted Drugs.

The synthesis and characterization of Pt(II) (1 and 2) and Ru(II) arene (3 and 4) or polypyridine (5 and 6) complexes is described. With the aim of having a functional group to form bioconjugates, one uncoordinated carboxyl group has been introduced in all complexes. Some of the complexes were selected for their potential in photodynamic therapy (PDT). The molecular structures of complexes 2 and 5, as well as that of the sodium salt of the 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine ligand (cptpy), were determined by X-ray diffraction. Different techniques were used to evaluate the binding capacity to model DNA molecules, and MTT cytotoxicity assays were performed against four cell lines. Compounds 3, 4, and 5 showed little tendency to bind to DNA and exhibited poor biological activity. Compound 2 behaves as bonded to DNA probably through a covalent interaction, although its cytotoxicity was very low. Compound 1 and possibly 6, both of which contain a cptpy ligand, were able to intercalate with DNA, but toxicity was not observed for 6. However, compound 1 was active in all cell lines tested. Clonogenic assays and apoptosis induction studies were also performed on the PC-3 line for 1. The photodynamic behavior for complexes 1, 5, and 6 indicated that their nuclease activity was enhanced after irradiation at λ = 447 nm. The cell viability was significantly reduced only in the case of 5. The different behavior in the absence or presence of light makes complex 5 a potential prodrug of interest in PDT. Molecular docking studies followed by molecular dynamics simulations for 1 and the counterpart without the carboxyl group confirmed the experimental data that pointed to an intercalation mechanism. The cytotoxicity of 1 and the potential of 5 in PDT make them good candidates for subsequent conjugation, through the carboxyl group, to "selected peptides" which could facilitate the selective vectorization of the complex toward receptors that are overexpressed in neoplastic cell lines.

Understanding growth and development of three short-season grain legumes for improved adaptation in semi-arid Eastern Kenya

Short-season grain legumes play an important role in smallholder farming systems as source of food and to improve soil fertility through nitrogen fixation. However, it is not clearly understood how these diverse legumes contribute to the resilience of such systems in semi-arid environments. We describe the growth, development and resource-use efficiency (focusing on radiation, RUE) of three promising short-season grain legumes: common bean (Phaseolus vulgaris L.), cowpea (Vigna unguiculata (L.) Walp.) and lablab (Lablab purpureus (L.) Sweet). Two field experiments were conducted during the short rains of 2012–13 and 2013–14 in Eastern Kenya. In the first experiment, the legumes were grown at three plant densities (low, medium, high); in the second experiment, they were subjected to three water regimes (rainfed, partly irrigated, fully irrigated). Phenological development was monitored and biomass accumulation, leaf area index and fractional radiation interception were measured repeatedly during growth; grain yield was measured at maturity. Harvest index and RUE were calculated from these data. Common bean had the shortest growing period (70 days), the most compact growth habit and relatively high RUE but limited grain yield (1000–1900 kg ha–1), thereby proving more suitable for cultivation in areas with restricted cropping windows or in intercropping systems. Cowpea had a longer growing period (90 days) and a spreading growth habit leading to high light interception and outstanding grain yields under optimal conditions (1400–3050 kg ha–1). Lablab showed stable RUE values (0.76–0.92 g MJ–1), was relatively unaffected by limited water availability and had a comparatively long growing period (100 days). Lablab grain yields of ~1200–2350 kg ha–1 were obtained across all water regimes, indicating a high potential to cushion climatic variability. Planting density strongly influenced the production success of cowpea and lablab, with high plant densities leading to vigorous growth habit with low podset establishment. Such information on temporal and spatial differences in growth, development and resource-use efficiency is highly valuable for crop-modelling applications and for designing more resilient farming systems with short-season grain legumes.

Small differences in structure, a large difference in activity – Comparing a new Ru(II)-3-hydroxyiminoflavanone complex with analogous Ru(II) compounds

Ruthenium compounds are a class of potential anticancer agents in a field with many emerging metal-based drugs and drug candidates. This work presents the synthesis and structural evaluation of a new Ru(II) complex of 3-hydroxyiminoflavanone with spectroscopic and crystallographic methods. Its cytostatic and hemostatic activity, as well as its behavior in solution, are compared with those of two previously described, cytotoxic Ru(II) complexes with C2-substituted 3-iminoflavanones. The synthesis of this compound results in the oxidation of one of the two coordinated 3-hydroxyiminoflavanones to 3-nitrosoflavone and reduction of Ru(III) to Ru(II). The obtained complex has moderate to low toxicity towards five human cancer cell lines, unlike similar ruthenium compounds. The article attempts to account for the difference on the basis of structural differences, solution UV–Vis studies and theoretical evaluation. As none of the tested compounds seriously alter hemostasis or red blood cell integrity in vitro, they might be suitable for further in vitro and in vivo testing.

Spectroscopic, DFT, magnetic and biological activity evaluation of Pd(II), Pt(II) and Ru(III) complexes of Nitazoxanide

[M(NTZ)Cl2] (M=Pd(II) (1), Pt(II) (2) and NTZ=Nitazoxanide) and [Ru(NTZ)Cl3(OH2)] (3) complexes have been synthesized and characterized by elemental analysis, thermogravimetric analysis, IR, 1HNMR, conductance and magnetic measurements. NTZ is coordinated to the metal ions as a bidentate ligand via the N-atom of the thiazole ring and amide CO. The susceptibility of Staphylococcus aureus and Escherichia coli towards NTZ and its complexes has been evaluated. The calculated electronic structures and the related electronic transitions have been obtained at TD-DFT/B3LYP/LANL2DZ level of theory. Upon the chelation, the value of the natural charge of Ru(III) ion (+0.182e) was found to be lower than those of Pd(II) and Pt(II) ions (∼+0.398e) in their complexes, which reflects the higher complexation ability of NTZ towards the high oxidation state and low-d-orbital population metal ion. Complex 3 is existing in a low-spin octahedral arrangement. The DC magnetic measurements in terms of Weiss constant revealed the presence of the intermolecular interactions among the spin carriers. The low stability of 1–3inDMSO and the rate of the releasing of NTZ was the factor which reproduces the order of the toxicity (NTZ>2>3>1) against the tested microbes.

Synthesis, characterization and biological evaluation of novel Ru(II)–arene complexes containing intercalating ligands

Three new ruthenium(II)–arene complexes, namely [(η6-p-cymene)Ru(Me2dppz)Cl]PF6 (1), [(η6-benzene)Ru(Me2dppz)Cl]PF6 (2) and [(η6-p-cymene)Ru(aip)Cl]PF6 (3) (Me2dppz=11,12-dimethyldipyrido[3,2-a:2′,3′-c]phenazine; aip=2-(9-anthryl)-1H-imidazo[4,5-f] [1,10] phenanthroline) have been synthesized and characterized using different spectroscopic techniques including elemental analysis. The complexes were found to be well soluble and stable in DMSO. The biological activity of the three complexes was tested in three different human cancer cell lines (A549, MDA-MB-231 and HeLa) and in one human non-cancerous cell line (MRC-5). Complexes 1 and 3, carrying η6-p-cymene as the arene ligand, were shown to be toxic in all cell lines in the low micromolar/subnanomolar range, with complex 1 being the most cytotoxic complex of the series. Flow cytometry analysis revealed that complex 1 caused concentration- and time-dependent arrest of the cell cycle in G2-M and S phases in HeLa cells. This event is followed by the accumulation of the sub-G1 DNA content after 48h, in levels higher than cisplatin and in the absence of phosphatidylserine externalization. Fluorescent microscopy and acridine orange/ethidium bromide staining revealed that complex 1 induced both apoptotic and necrotic cell morphology characteristics. Drug-accumulation and DNA-binding studies performed by inductively coupled plasma mass spectrometry in HeLa cells showed that the total ruthenium uptake increased in a time- and concentration-dependent manner, and that complex 1 accumulated more efficiently than cisplatin at equimolar concentrations. The introduction of a Me2dppz ligand into the ruthenium(II)-p-cymene scaffold was found to allow the discovery of a strongly cytotoxic complex with significantly higher cellular uptake and DNA-binding properties than cisplatin.

Mechanism of N,N,N-Amide Ruthenium(II) Hydride Mediated Acceptorless Alcohol Dehydrogenation: Inner-Sphere β-H Elimination versus Outer-Sphere Bifunctional Metal–Ligand Cooperativity

The reversible transformations between ketones and alcohols via sequential hydrogenation–dehydrogenation reactions are efficiently achieved using a single precatalyst HRu(bMepi)(PPh3)2 (bMepi = 1,3-bis(6′-methyl-2′-pyridylimino)isoindolate). The catalytic mechanism of HRu(bMepi)(PPh3)2 mediated acceptorless alcohol dehydrogenation (AAD) has been investigated by a series of kinetic and isotopic labeling studies, isolation of intermediates, and evaluation of Ru(b4Rpi)(PPh3)2Cl (R = H, Me, Cl, OMe, OH) complexes. Two limiting dehydrogenation scenarios are interrogated: inner-sphere β-H elimination and outer-sphere bifunctional double hydrogen transfer. Isotopic labeling experiments demonstrated that the proton and hydride transfer in a stepwise manner. Catalyst modifications suggest that the imine group on the bMepi pincer scaffold is not necessary for catalytic alcohol dehydrogenation. Evaluation of the kinetic experiments and catalyst modifications suggests a pathway whereby HRu(bMepi)(PPh3)2 operates via ...

Synthesis, characterization, DNA/protein binding and in vitro cytotoxic evaluation of new Ru(III) complexes containing aroylhydrazone ligands: Does hydrogen bonding influence the coordination behavior of hydrazones?

A new set of ruthenium(III) aroylhydrazone complexes [RuCl2(PPh3)2(HL1)] (1) and [RuCl(PPh3)2(L2)] (2) were synthesized by reacting salicylaldehyde p-toluic acid hydrazone (H2L1) or 2-hydroxy-acetophenone p-toluic acid hydrazone (H2L2) and [RuCl3(PPh3)3] precursor complex and characterized. Single crystal X-ray diffraction data of these complexes revealed a distorted octahedral geometry around ruthenium ions fulfilled by NOP2Cl2 atoms and NO2P2Cl atoms, respectively. Though the ligands look similar in respect of structure and donor sites, the existence of H-bonding between the phenolic –OH and N2 nitrogen of the coordinated ligand H2L1 as revealed by the single crystal data of complex 1 is attributed to the non-involvement of the hydroxyl group in coordination to the ruthenium ion which is in sharp contrast to the behaviour exhibited by the ligand H2L2 in complex 2. As a result, the ligand H2L1 acted as a monobasic bidentate against the dibasic tridentate behaviour of the ligand H2L2. Binding interactions of these complexes with calf thymus-DNA (CT-DNA) estimated by absorption and emission spectroscopy did demonstrate the intercalative mode of binding. The capability of complexes 1 and 2 to bind with bovine serum albumin (BSA) protein was monitored by quenching of tryptophan and tyrosine residues using UV–Vis, fluorescence and synchronous fluorescence methods. Further, in vitro cytotoxicity of the complexes was carried out using MTT, lactate dehydrogenase (LDH), Nitric oxide (NO), reactive oxygen species (ROS) and propidium iodide (PI) staining assays against non-small cell lung cancer cell line (A549).

Evaluation of trimetallic Ru(II)- and Os(II)-Arene complexes as potential anticancer agents

Schiff-base ligands, tris-2-(salicylaldimine ethyl)amine and tris-2-(2-pyridylimine ethyl)amine (1 and 2) were prepared and complexed to Ru(II) and Os(II) entities to form new trimetallic complexes (3–10). The complexes are air- and moisture-stable and have been characterized fully using elemental analysis, FT-IR and NMR spectroscopy as well as HR-ESI-TOF-MS spectrometry. Related mononuclear analogues (11–14) were also prepared via the Schiff-base condensation reaction of propyl amine and the appropriate aldehyde to form propysalicylaldimine and propyl-2-pyridylimine ligands. Upon complexation with the respective metal dimers, ([OsCl2(p-cym)]2 and [OsBr2(p-cym)]2) complexes (11–14) formed and were characterized by elemental analysis, NMR, FT-IR spectroscopy and mass spectrometry. The cytotoxicity of the trimetallic complexes (3–10) and their mononuclear analogues were established against human osteosarcoma (MG63), human ovarian (A2780cisR; cisplatin-resistant) cancer cells and model human non-cancerous cells (KMST6, fibroblast). All the complexes exhibited moderate to high anti-cancer activities and the most potent complexes were further evaluated for their ability to inhibit DNA topoisomerase I (Topo I) – an enzyme key to cellular genetic processes, such as DNA replication and transcription.

Synthesis, characterization, and biological evaluation of new Ru(II) polypyridyl photosensitizers for photodynamic therapy.

Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)](2+) (2) (DIP = 4,7-diphenyl-1,10-phenanthroline, bdt = 1,2-benzenedithiolate, dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine), ptpy = 4'-phenyl-2,2':6',2″-terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and phototoxic index (PI) of 2 (IC50(light): 25.3 μM, 420 nm, 6.95 J/cm(2); PI >4) and particularly of 1 (IC50(light): 0.62 μM, 420 nm, 6.95 J/cm(2); PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic acid. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (1) and by inductively coupled plasma mass spectrometry (1 and 2). Their phototoxicity was also determined against the Gram-(+) Staphylococcus aureus and Gram-(-) Escherichia coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm(2)) against Gram-(+) (S. aureus; >6 log10 CFU reduction) and, for 2, also against Gram-(-) E. coli (>4 log10 CFU reduction).

Synthesis and evaluation of new polynuclear organometallic Ru(ii), Rh(iii) and Ir(iii) pyridyl ester complexes as in vitro antiparasitic and antitumor agents

New polynuclear organometallic Platinum Group Metal (PGM) complexes containing di- and tripyridyl ester ligands have been synthesised and characterised using analytical and spectroscopic techniques including (1)H, (13)C NMR and infrared spectroscopy. Reaction of these polypyridyl ester ligands with either [Ru(p-cymene)Cl2]2, [Rh(C5Me5)Cl2]2 or [Ir(C5Me5)Cl2]2 dimers yielded the corresponding di- or trinuclear organometallic complexes. The polyaromatic ester ligands act as monodentate donors to each metal centre and this coordination mode was confirmed upon elucidation of the molecular structures for two of the dinuclear complexes. The di- and trinuclear PGM complexes synthesized were evaluated for inhibitory effects on the human protozoal parasites Plasmodium falciparum strain NF54 (chloroquine sensitive), Trichomonas vaginalis strain G3 and the human ovarian cancer cell lines, A2780 (cisplatin-sensitive) and A2780cisR (cisplatin-resistant) cell lines. All of the complexes were observed to have moderate to high antiplasmodial activities and the compounds with the best activities were evaluated for their ability to inhibit formation of synthetic hemozoin in a cell free medium. The in vitro antitumor evaluation of these complexes revealed that the trinuclear pyridyl ester complexes demonstrated moderate activities against the two tumor cell lines and were also less toxic to model non-tumorous cells.

Evaluation of RU 486 as a Labour Inducing Agent in Term Pregnancy in Western Uttar Pradesh

Evaluation of RU 486 as a Labour Inducing Agent in Term Pregnancy in Western Uttar Pradesh

Evaluation of (arene)Ru(II) complexes of curcumin as inhibitors of dipeptidyl peptidase IV

Curcumin, the main component of Curcuma longa, shows an anti-hyperglycemic effect and improved insulin sensitivity. This action may be attributed at least in part to its anti-inflammatory properties and also to its possible interaction with dipeptidyl peptidase-4 (DPPIV), the enzyme that the conversion of glucagon-like peptide-1 (GLP-1), responsible for glucose tolerance into inactive GLP-1. In this work we evaluated the inhibitory activities of a series of different arene-Ru(II)-curcumin complexes on bovine kidney dipeptidyl peptidase-4 (DPPIV). We studied also the interaction of these inhibitors on the enzyme with fluorescence studies displaying the binding poses with molecular docking studies. Specifically organometallic ruthenium(II) complexes of general formula [(η(6)-arene)Ru(curcuminato)Cl], with arene being p-(i)PrC6H4Me (1), C6H6 (2), and C6Me6 (3), were evaluated for their inhibition activity toward the mammalian enzyme. Among them, 2 suppressed DPPIV activities more potently (Ki=20.2(±0.8)μM) than 1, 3, or free curcumin, and all complexes showed an antioxidant activity as free curcumin. As shown from our docking simulations a putative binding site of the compound 2 was found on subdomains S1 and S2 of DPP-IV, where S1 hydrophobic pocket includes catalytic residues and is the primary determinant of substrate specificity for the enzyme. Collectively, our results demonstrate that the complexation of curcumin with ruthenium(II) could be a promising starting point for the development of curcumin-based DPPIV inhibitors.