In vitro biological activity of cobalt(II) complexes with salicylaldimine ligands in microbial and cancer cells.

Background: More studies using cobalt complexes as drugs are needed. Results: The drug action of two cobalt salicylaldimines was determined. The complexes and amphotericin B (20 mg/ml) inhibited Candida albicans at 9-15 and 21 mm. This concentration of both ligands inhibited Staphylococcus aureus at 10 mm and one ligand inhibited Escherichia coli at 9 mm, but the complexes and ampicillin inhibited four bacteria at 9-20 and 21-26 mm. The ligands were inactive against cancer and normal cells, but the complexes and doxorubicin provided IC50 values of 28.18-54.19 and 9.66 µM against MCF-7 cells and 15.76-20.49 and 36.42 µM against BHK cells. Conclusion: The ligands' activity was much improved by complexation, although they remained substandard.

Supramolecular Coronation of Platinum(II) Complexes by Macrocycles: Structure, Relativistic DFT Calculations, and Biological Effects.

Platinum-based anticancer drugs are actively developed utilizing lipophilic ligands or drug carriers for the efficient penetration of biomembranes, reduction of side effects, and tumor targeting. We report the development of a supramolecular host-guest system built on cationic platinum(II) compounds bearing ligands anchored in the cavity of the macrocyclic host. The host-guest binding and hydrolysis process on the platinum core were investigated in detail by using NMR, MS, X-ray diffraction, and relativistic DFT calculations. The encapsulation process in cucurbit[7]uril unequivocally promotes the stability of hydrolyzed dicationic cis-[PtII(NH3)2(H2O)(NH2-R)]2+ compared to its trans isomer. Biological screening on the ovarian cancer lines A2780 and A2780/CP shows time-dependent toxicity. Notably, the reported complex and its ß-cyclodextrin (ß-CD) assembly achieve the same cellular uptake as cisplatin and cisplatin@ß-CD, respectively, while maintaining a significantly lower toxicity profile.

Anti-inflammatory and antioxidant properties of chemical constituents of Broussonetia papyrifera.

Extensive phytochemical analysis of the CHCl3-soluble part of an ethanolic extract of branches and twigs of Broussonetia papyrifera led to the isolation of fourteen compounds, including a novel 5,11-dioxabenzo[b]fluoren-10-one derivative named broussofluorenone C (12). The isolated compounds 1-14 were characterized based on their NMR and HRMS data, and examined for their anti-inflammatory activities in LPS-stimulated THP-1 cells as well as for their cellular antioxidant effects. Compounds 7-10 and 12 showed inhibitory effects on NF-κB/AP-1 activation and compounds 7-9 were subsequently confirmed to suppress the secretion of both IL-1ß and TNF-α in LPS-stimulated THP-1 cells more significantly than the prednisone used as a positive control. In the CAA assay, compound 10 exhibited the greatest antioxidant effect, greater than that of the quercetin used as a positive control. The results show possible beneficial effects and utilization of B. papyrifera wood in the treatment of inflammatory diseases as well as oxidative stress.

Transformations of the natural cytokinin N6-isopentenyladenine in aqueous acidic media: structural aspects.

N6-Isopentenyladenine (L1) was subjected to variously acidic media in 0.1 M, 1 M and 2 M HCl. In dependence on the acidity of the medium, the formation of three main acid hydrolysis products, involving the N6-isopentenyladeninium (HL1) (1), 7,8,9,10-tetrahydro-7,7-dimethyl-3H-pyrimido[2,1-i]purin-6-ium (HL2) (2) or 5-amino-4-(4,4-dimethyl-3,4,5,6-tetrahydropyrimidin-2-yl)-imidazolium (H(2)L3) (3-5) cations, were determined and characterized by multinuclear solution-state NMR spectroscopy and in the solid state by single crystal X-ray analysis. The coordination abilities of these transformation products have been also investigated. The compounds of the compositions [Zn(HL1)Cl(3)]·H(2)O (1), [Zn(3)(HL2)(2)Cl(8)] (2), (H(2)L3)[CuCl(4)] (4) and (H(2)L3)[ZnCl(4)] (5) have been prepared in dependence on the acidity of the medium used by the reactions of L1 with ZnCl(2)·1.5H(2)O or CuCl(2)·2H(2)O. Based on the NMR spectroscopic and X-ray crystallographic results, the mechanism of transformation of L1 in the acidic medium, involving the protonation, cyclization and ring fission, has been suggested.

Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families.

BACKGROUND: The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6-8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors. METHODOLOGY/PRINCIPAL FINDINGS: Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins. CONCLUSIONS/SIGNIFICANCE: We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins.

(µ-5-Carboxy-benzene-1,3-dicarboxyl-ato-κO:O)bis-[bis-(2,2'-bipyridine-κN,N')copper(II)] 5-carboxy-benzene-1,3-dicarboxyl-ate 2,2'-bipyridine solvate trideca-hydrate.

The asymmetric unit of the title complex, [Cu(2)(C(9)H(4)O(6))(C(10)H(8)N(2))(4)](C(9)H(4)O(6))·C(10)H(8)N(2)·13H(2)O, comprises two formula units. The two Cu(II) centres are bridged by a 5-carb-oxy-benzene-1,3-dicarboxyl-ate (Hbtc) ligand. Each of the metal centres is bonded to four N atoms of two bidentate 2,2'-bipyridine ligands (bpy) and one O atom of the Hbtc ligand in a highly distorted square-pyramidal geometry. The secondary structure is stabilized by a variety of O-H⋯O hydrogen bonds and π-π stacking inter-actions connecting the complex cations, Hbtc anions, bpy and water mol-ecules of crystallization. Three water molecules are disordered over two positions, with site occupancy factors of ca 0.8 and 0.2.

Mixed ligand complexes of platinum(II) and palladium(II) with cytokinin-derived compounds Bohemine and Olomoucine: X-ray structure of [Pt(BohH+-N7)Cl(3)].9/5H2O [Boh=6-(benzylamino)-2-[(3-(hydroxypropyl)-amino]-9-isopropylpurine, Bohemine].

The new square-planar Pt(II) and Pd(II) complexes with cytokinin-derived compounds Bohemine and Olomoucine, having the formulae [Pt(BohH(+))Cl(3)].H(2)O (1), [Pt(Boh)(2)Cl(2)].3H(2)O (2), [Pt(Boh-H)Cl(H(2)O)(2)].H(2)O (3), [Pt(OloH(+))Cl(3)].H(2)O (4), [Pd(BohH(+))Cl(3)].H(2)O (5), [Pd(Boh)Cl(2)(H(2)O)] (6), [Pd(Boh-H)Cl(H(2)O)].EtOH (7) and [Pd(OloH(+))Cl(3)].H(2)O (8), where Boh=6-(benzylamino)-2-[(3-(hydroxypropyl)amino]-9-isopropylpurine and Olo=6-(benzylamino)-2-[(2-(hydroxyethyl)amino]-9-methylpurine, have been synthesized. The complexes have been characterized by elemental analyses, IR, FAB+ mass, 1H, 13C and 195Pt NMR spectra, and conductivity data. The molecular structure of the complex [Pt(BohH(+)-N7)Cl(3)].9/5H(2)O has been determined by an X-ray diffraction study. Results from physical studies show that both Bohemine and Olomoucine are coordinated to transition metals through the N(7) atom of purine ring in all the complexes. The prepared compounds have been tested in vitro for their possible cytotoxic activity against G-361 (human malignant melanoma), HOS (human osteogenic sarcoma), K-562 (human chronic myelogenous leukemia) and MCF-7 (human breast adenocarcinoma) cell lines and IC(50) values have been also determined for all the complexes. IC(50) values estimated for the Pt(II)-Bohemine complexes (2.1-16 microM) allow us to conclude that they could find utilization in antineoplastic therapy. Thus, from a pharmacological point of view, Pt(II) complexes of Bohemine may represent compounds for a new class of antitumor drugs.