Poly[[tetra­aquabis­(μ-hydroxy­acetato-κ4 O 1,O 2:O 1,O 1′)-μ2-sulfato-κ2 O:O′-dicadmium(II)] monohydrate]

The title compound, {[Cd2(C2H3O3)2(SO4)(H2O)4]·H2O}n, was obtained unintentionally in a transmetallation reaction. The crystal structure contains a two-dimensional metal–organic framework based on CdII–(μ-hydroxy­acetato-κ4 O 1,O 2:O 1,O 1′)–CdII zigzag chains joined together by bridging SO4 anions. The resulting layers are shifted with respect to each other and are stacked along the c axis. Their construction is supported by hydrogen bonds between water molecules and between water molecules and carboxylate or sulfate groups. Neighbouring layers are bridged by hydrogen bonds between the hydroxyl substituent and a sulfate anion. The sulfate anion and solvent water mol­ecule are located on twofold axes. The results demonstrate that care must be taken when preparing ethyl­enediamine­tetra­acetic acid-type complexes by transmetallation, in order to avoid precipitation of metal complexes with the α-hydroxy­acetate ligand

Growth Effects of Some Platinum(II) Complexes with Sulfur-Containing Carrier Ligands on MCF7 Human Breast Cancer Cell Line upon Simultaneous Administration with Taxol

The platinum (II)complexes, cis-[PtCl2(CH3SCH2CH2SCH3)] (Pt1), cis-[PtCl2(dmso)2] (dmso is dimethylsulfoxide; Pt2) and cis-[PtCl2(NH3)2] (cisplatin), and taxol (T) have been tested at different equimolar concentrations. Cells were exposed to complexes for 2 h and left to recover in fresh medium for 24, 48 or 72 h. Growth inhibition was measured by tetrazolium WST1 assay Analyses of the cell cycle, and apoptosis were performed by flow cytometry, at the same exposure times. The IC50 value of each platinum(II) complex as well as combination index (CI; platinum(II) complex + taxol) for various cytotoxicity levels were determined by median effects analysis

Silver(I) Complexes with Clinically Used Azoles: Synthesis, Structural Characterization and Antimicrobial Evaluation

Recently, we synthesized silver(I) complex with the antifungal agent itraconazole, which showed improved anti-Candida potential and therapeutic safety in comparison to itraconazole and rescued zebrafish embryos affected by lethal C. albicans infection, when used in safe doses. Inspired by these results, in the present study, three new silver(I) complexes with clinically used azoles, econazole (ecz), clotrimazole (ctz) and voriconazole (vcz), [Ag(ecz)2]SbF6 (Ag1), [Ag(ctz)2]SbF6 (Ag2) and {[Ag(vcz)2]SbF6}n (Ag3) were synthesized and structurally characterized by elemental microanalysis, mass spectrometry, spectroscopy (1H NMR, IR and UV-Vis), cyclic voltammetry, molar conductivity measurements, and single crystal X-ray diffraction analysis. The spectroscopic and crystallographic results revealed that, in the synthesized silver(I) complexes, azole ligands are monodentately coordinated to the Ag(I) ion through the nitrogen atom forming [Ag(azole)2]+ complex cation. The antimicrobial effect of complexes and azole ligands was evaluated against different Candida species, as well as Gram-positive and Gram-negative bacteria. The synthesized complexes Ag1-3 exhibited good to moderate antimicrobial activity being, in most cases, more active than the corresponding azole ligands. Complexes Ag2 and Ag3 also showed strong inhibitory activity against C. albicans biofilm formation and strong inhibition of C. albicans filamentation at subinhibitory concentrations

DNA/BSA interaction of platinum(II) complexes with phenothiazine and N-methylphenothiazine

In the present study, the interactions of two platinum(II) complexes of the general formula cis-[PtCl2(L)(CH3CN)], L is phenothiazine (phtz, Pt1) and N-methylphenothiazine (NMephtz, Pt2) with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) were studied by fluorescence emission spectroscopy to check their binding affinity towards these biomolecules for possible insights into the mode of their biological activity. A remarkable decrease in BSA fluorescence intensity after the addition of the complexes Pt1 and Pt2 and high values of the binding constants are in accordance with their high affinity toward this protein. On the other hand, the low binding affinity of the studied platinum(II) complexes to ct-DNA-EthBr system (EthBr is ethidium bromide, a well-known DNA intercalator) was observed. This has indicated that proteins could be more favorable binding sites for these platinum(II) complexes in comparison to the nucleic acids. Interestingly, Pt1 complex has shown a higher binding affinity toward DNA than Pt2, while the latter complex is a more efficient BSA binder.Publishe

Different coordination abilities of 1,7- and 4,7-phenanthroline in the reactions with copper(II) salts: Structural characterization and biological evaluation of the reaction products

The reactions between equimolar amounts of CuX2 (X = NO3− and CF3SO3−) and two aromatic nitrogen-containing heterocycles differing in the position of nitrogen atoms, 1,7- and 4,7-phenanthroline (1,7- and 4,7-phen), were performed in ethanol/methanol at room temperature. When CuX2 salts were mixed with 4,7-phen, two copper(II) complexes, [Cu(NO3)2(4,7-Hphen)2](NO3)2 (1) and [Cu(CF3SO3)(4,7- phen)2(H2O)2]CF3SO3 (2), were formed. On the other hand, in the reaction of CuX2 salts with 1,7-phen, only 1,7-HphenNO3 (3a/b) and 1,7-HphenCF3SO3 (4) were obtained as the final products. The obtained products 1–4 were characterized by spectroscopic and X-ray diffraction techniques. In the copper(II) complexes 1 and 2, the coordination geometry around the Cu(II) ion is distorted octahedral and square pyramidal, respectively. The antimicrobial potential of the copper(II) complexes 1 and 2 and corresponding compounds used for their synthesis were assessed against four different bacterial species and Candida albicans, displaying moderate growth inhibiting activity. The cytotoxic properties of the investigated complexes were also evaluated against the normal human lung fibroblast cell line (MRC-5) indicating moderate, yet more pronounced cytotoxicity than antimicrobial properties

Antimicrobial activity and DNA/BSA binding study of new silver(I) complexes with 1,8-naphthyridine

Silver(I) compounds are well known for their pharmacological applications as antibiotics and have been also evaluated as potential anticancer agents. The use of simple silver(I) salts, such as AgNO3, as an antimicrobial agent, has been limited due to the formation of AgCl precipitate under the physiological conditions, preventing a major part of Ag(I) ions to reach the infected site. On the other hand, a slow and maintainable release of Ag(I) ion into the infected cell or tissue could be achieved by its administration in the form of complexes. Among different classes of ligands used for the synthesis of biologically active silver(I) complexes, a special attention was devoted to the aromatic nitrogen-containing heterocycles. Considering this, in the present study, we have synthesized two new silver(I) complexes with 1,8-naphthyridine (1,8-naph), polynuclear [Ag(CF3SO3)(1,8-naph)]n (Ag1) and dinuclear [Ag(1,8-naph)(H2O)]2(PF6)2 (Ag2), and evaluated their antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as Candida spp. The obtained results revealed that these silver(I) complexes showed significant activity toward the Gram-positive Staphylococcus aureus and Candida spp. The values of binding constants of Ag1 and Ag2 to BSA are high enough to indicate their interaction to this biomolecule, but not so strong to prevent their release upon arrival to the target site. The partition coefficient (logP) values for Ag1 and Ag2 are -0.14 and 0.37, respectively, what is in accordance with those for pharmacophores in the Comprehensive Medicinal Chemistry database. Тhe investigated silver(I) complexes inside the cell could interact with DNA through the non-intercalative (electrostatic) mode.6th International Electronic Conference on Medicinal Chemistry session General: Presentation

Improvement of antifungal activity and therapeutic profile of fluconazole by its complexation with copper(II) and zinc(II) ions. Complex characterization and antimicrobial activity studies

Over the last few decades, invasive fungal infections represent a serious problem for modern-day healthcare. Aspergillus, Candida and Cryptococcus species are the most common pathogens causing life-threatening infections. Therapeutic options for the treatment of fungal infections are presently limited to only four classes of compounds and each of these drug classes has significant therapeutic limitations, including serious toxic-side effects, resistance development and limited routes of administration. In order to overcome resistance of the clinically used antifungal triazole agents, we synthesized zinc(II) and copper(II) complexes with fluconazole (flz), {[ZnCl2(flz)2]·2C2H5OH}n (1) and {[CuCl2(flz)2].5H2O}n (2). These complexes were obtained from the reactions between ZnCl2 or CuCl2·2H2O with this antifungal agent in 1 : 2 molar ratio in ethanol at room temperature. The compounds were characterized by elemental analysis, NMR, IR and UV-Vis spectroscopy and mass spectrometry. The crystal structure of complex 1 was determined by a single-crystal X-ray diffraction analysis. The antimicrobial effect of both complexes and fluconazole was evaluated against different Candida species as well as Gram-positive and Gram-negative bacteria by means of minimal inhibitory concentrations (MICs). The obtained results have shown that, in most cases, the coordination of fluconazole to Zn(II) and Cu(II) ions leads to the enhancement of its antifungal activity. Both complexes showed strong inhibitory activity against C. albicans biofilm formation at concentrations lower than MIC values, as well as strong inhibition of C. albicans filamentation.6th International Electronic Conference on Medicinal Chemistr

DNABSA interactions and biological activity of prodigiosin and its copper(II) complex

Prodigiosin (PG) is a red biopigment produced as a secondary metabolite by microorganisms such as Serratia marcescens and Streptomyces. In recent years, this tripyrrole compound has attracted an increasing attention due to its antibacterial, antimalarial, and immunosuppressive activities [1]. It is also known for its antitumor activity, inducing the cell death by apoptosis in different human cancer cell lines [2]. Considering this, in the present study, we investigated the interactions of prodigiosin and its copper(II) complex (CuPG; the structural formula is presented below), whose crystal structure was determined previously [2], with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) by fluorescence emission spectroscopy to clarify their binding affinities toward these biomolecules. The antimicrobial activity of the synthesized CuPG complex and PG ligand was evaluated in vitro against various microorganisms that can lead to many infections. Moreover, CuPG and PG were evaluated in a cell viability assay on a healthy MRC-5 cell line, as well as a panel of MDA-MB-231, A549, A375, and HCT116 cancer cell lines.Book of abstract:16th International Symposium on Applied Bioinorganic Chemistry (16-ISABC) 11-14th June University of Ioannina Greec

Structural characterization and antitumor activity of platinum(II) complexes with phenothiazine and N-methylphenothiazine

Cisplatin is one of the most used anticancer agents, and along with carboplatin and oxaliplatin, is a part of more than 50% of clinically applied anticancer regimens [1]. However, the side effects of cisplatin are severe and include dose-limiting toxicity, such as neurotoxicity, nephrotoxicity and ototoxicity. Platinum(II) complexes with different structure from cisplatin provide many opportunities for design of novel antitumor drugs with improved pharmacological properties. Considering this, in the present study, new platinum(II) complexes with phenothiazine (phtz) and N-methylphenothiazine (N-Mephtz), [PtCl2(phtz)(CH3CN)] (1) and [PtCl2(N-Mephtz)(CH3CN)] (2), were synthesized. These complexes were characterized by elemental microanalysis, NMR (1H and 13C) and IR spectroscopic measurements, while the structure of complex 1 was determined by single-crystal X-ray diffraction analysis. The antitumor activity of the platinum(II) complexes was tested in vitro against a panel of human cancer cell lines, including A549 (lung cancer), A375 (melanoma, skin cancer), MDA-MB-231 (breast cancer), and HCT116 (colon cancer). To check the selectivity of the synthesized complexes 1 and 2, a healthy MRC-5 cell line (lung fibroblasts) was also included in this study.Book of abstract:16th International Symposium on Applied Bioinorganic Chemistry (16-ISABC) 11-14th June University of Ioannina Greec

Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection

Five novel silver(I) complexes with 4,7-phenanthroline (4,7-phen), [Ag(NO3-O)(4,7- phen-μ-N4,N7)]n (1), [Ag(ClO4-О)(4,7-phen-μ-N4,N7)]n (2), [Ag(CF3COO-O)(4,7- phen-μ-N4,N7)]n (3), [Ag2(H2O)0.58(4,7-phen)3](SbF6)2 (4) and {[Ag2(H2O)(4,7- phen-μ-N4,N7)2](BF4)2}n (5) were synthesized, structurally elucidated and biologically evaluated. These complexes showed selectivity towards Candida spp. in comparison to the tested bacteria and effectively inhibited the growth of four different Candida species, particularly of C. albicans strains, with minimal inhibitory concentrations (MICs) in the range of 2.0–10.0 μM. In order to evaluate the therapeutic potential of 1–5, in vivo toxicity studies were conducted in the zebrafish model. Based on the favorable therapeutic profiles, complexes 1, 3 and 5 were selected for the evaluation of their antifungal efficacy in vivo using the zebrafish model of lethal disseminated candidiasis. Complexes 1 and 3 efficiently controlled and prevented fungal filamentation even at sub-MIC doses, while drastically increased the survival of the infected embryos. Moreover, at the MIC doses, both complexes totally prevented C. albicans filamentation and rescued almost all infected fish of the fatal infection outcome. On the other side, complex 5, which demonstrated the highest antifungal activity in vitro, affected the neutrophils occurrence of the infected host, failed to inhibit the C. albicans cells filamentation and showed a poor potential to cure candidal infection, highlighting the importance of the in vivo activity evaluation early in the therapeutic design and development process. The mechanism of action of the investigated silver(I) complexes was related to the induction of reactive oxygen species (ROS) response in C. albicans, with DNA being one of the possible target biomolecules