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Purpose: Safety and toxicity evaluation of a nove liposome-encapsulated rapamycin formulation, intended for autoimmune ocular disorders. Methods: The formulation (60 and 180 µg for subconjunctival and 40 and 440 µg for intravitreal administration) were assessed through micronucleus polychromatic erythrocytes production, and irritability by HET CAM and pyrogenicity testing. Subconjunctival and intravitreal administration of the formulation were performed to evaluate subacute and acute toxicity, respectively. Shapiro Wilk and Kolmogorov-Smirnov tests were applied for normality. Pearson and Spearman Correlation tests for variable comparison. Differences between groups in biochemical and hematological parameters were evaluated by ANOVA test with significance determination by t-Holm-Sidak post-hoc test. A t-test was employed to compare independent, normally distributed variables. Numeric score was assigned to histopathological classification. Data was analyzed by a one way no parametric Kruskal-Wallis and the Mann-Whitney tests. Significance was considered when p

A family of pentacoordinated diorganotin(IV) compounds was synthesized and characterized through the advantageous approach of a multicomponent methodology involving the reaction between 4-(diethylamino)salicylaldehyde, dibutyltin oxide and including a series of l -amino acid fragments (alanine, valine, leucine, isoleucine, phenylalanine, tyrosine and methionine), all carried out in one-step, in excellent yields. Structures were elucidated by FTIR, HRMS and solution NMR (1H, 13C and 119Sn). Diorganotin(IV) derivatives crystallized easily and five unreported molecular structures were solved and analyzed by SC-XRD experiments; depending on the orientation of the alkyl residues different isomorphic arrays were found. Finally, pentacoordinated diorganotin(IV) complexes were tested against tumoral cell lines, HCT-15 (colon adenocarcinoma), HeLa (cervical uterine adenocarcinoma), MCF-7 (breast adenocarcinoma) and PC-3 (human prostate cancer) in order to evaluate their in vitro cytotoxicity.

In the present work, cell lines of different origin were exposed to BPA levels from food intake reported elsewhere. Specifically, we used an in vitro assay to determine cytotoxicity of BPA in three cell lines: MCF7 (breast cancer), PC3 (prostate cancer) and 3T3-L1 (mouse fibroblast). Cytotoxic effects were observed at concentrations higher than 50 μg/mL which is above the involuntary exposure level of BPA described before in fresh, canned and frozen foods and beverages. Furthermore, medial inhibitory concentrations (IC50) of 85.17 μg/mL and 88.48 μg/mL were observed for PC3 and 3T3-L1, respectively, and a slightly lower IC50 of 64.67 μg/mL for MCF7. These results highlight BPA's toxicity potential at current levels from food intake. The cell line-dependent divergent response to BPA reported herein is discussed.

Coordination compounds of cobalt(II), nickel(II), copper(II) and zinc(II) with L-5-hydroxytryptophan (L-5-HTP) were synthesized and characterized by elemental analysis, IR and UV–Vis-NIR spectroscopy, mass spectrometry and thermogravimetric analysis. The X-ray structure of the pure enantiomer ligand (L-5-HTP) was obtained. The ligand coordinates to the metal ions in an unidentate mode, where the donor atom is the oxygen from the carboxylic group. The intramolecular H-bond, N1H···O2, observed in the X-ray crystal structure of the free L-5-HTP, remains as a stabilization factor in all of the coordination compounds. Two types of geometries were adopted by the metal centers: tetrahedral and octahedral. In vitro antiadipogenic studies of the coordination compounds showed that the tetrahedral cobalt(II) and copper(II) complexes presented potential antiobesity properties.

Coordination compounds of nickel(II), palladium(II) and platinum(II) with tioconazole (tcnz) were synthesized and characterized by infrared, UV-Vis-NIR, elemental analysis, molar conductivity, magnetic susceptibility, mass spectrometry, NMR spectroscopy and X- ray diffraction. Tioconazole presented a monodentate coordination mode, through the nitrogen atom of the imidazolic ring. The NiII compounds stabilized an octahedral geometry. In [Ni(tcnz)2(NO3)2].H2O the coordinated nitrate presented a bidentate coordination mode, while for the [Ni(tcnz)2(OAc)2].3H2O compound, the acetate behaves as a bridging ligand. When different molar ratios were used on the reaction synthesis, three or six ligands were coordinate to the nickel(II) atom, [Ni(tcnz)3Br2(H2O)], [Ni(tcnz)6]Cl2 and [Ni(tcnz)6]Br2. The palladium(II) and platinum(II) compounds, [Pd(tcnz)2Cl2], [Pt(tcnz)2Cl2].2H2O and [Pd(tcnz)2(OAc)2], stabilized a trans-square planar geometry. The compounds [Ni(tcnz)6]X2 give place to 3D supramolecular arrangements through hydrogen bonding (X∙∙∙H, X = Cl and Br) and p∙∙∙p stacking interactions, between the six membered rings of neighbouring molecules. The in vitro cytotoxic activity of the synthesized compounds was studied in four different human carcinoma cell lines: HCT-15 (colon), HeLa (cervix-uterine), MCF-7 (breast) and PC-3 (prostate).

A series of new coordination compounds of cobalt(II), copper(II) and zinc(II) with heterocyclic ester derivatives (ethyl 4-methyl-5-imidazole-carboxylate (emizco), 1-(2-(phenylsulphonyl)ethyl)-4-imidazole carboxylate (semizco)) and methyl 5-(propylthio)-2-benzimidazolecarbamate (albendazole, abz) were synthesized. They were fully characterized by different techniques such as IR, UV-Vis-NIR, elemental analysis, molar conductivity and magnetic susceptibility. Additionally, X-ray crystal structures of semizco and its [Co(semizco)2Cl2]·2CH3CN 10, [Co(smmizco)2Br2]·2CH3CN 11 and [Cu(semizco)2Br2] 15 coordination compounds are analyzed. These compounds present lone pair SO⋯π interactions between the sulfone and the imidazolic ring. These ligands showed three coordination modes: monodentate, through an imidazolic nitrogen atom, or a bidentate chelating mode by a nitrogen and an oxygen atom from the ester group. The different coordination modes and the number of coordinated ligands gave rise to tetrahedral and octahedral compounds, or for [Cu(semizco)(μ-Br)Br]n·0.5H2O 7 a square base pyramidal geometry. A cytotoxic study was carried out with the free ligands and their copper(II) and zinc(II) halide coordination compounds on HeLa (cervix-uterine), MCF-7 (breast), HCT-15 (colon), PC3 (prostate) human carcinoma cell lines and L929 mouse fibroblast (healthy cells). A TUNEL assay (terminal deoxynucleotidyl transferase dUTP nick end labeling) was performed with the most active copper(II) compounds to determine if cell death was by apoptosis.

The enzyme-mediated grafting of tert-butylhydroquinone (TBHQ) onto chitosan and further crosslinking to agave inulin (agavin) has been successfully achieved in a mild and non-toxic two-step route. The resulting products were characterized by nuclear magnetic resonance (NMR) and Infra-red spectroscopies to assess the molecular structure. The study of acute oral toxicity in mice revealed no adverse short-term effects of consumption in the synthesized materials with non-toxicity evidence until 2000 mg/kg through an oral acute administration. Importantly, this study proves that the compound maintains the radical scavenging capacity of the phenolic antioxidant upon ferric-reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays with a measured half-maximal inhibitory concentration (IC50) for the best case of 1.54 g/L based on inhibition of 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid diammonium salt (ABTS). Additionally, the novel compound presented high prebiotic activities as ascertained in the presence of lactic acid bacteria (LAB).

Coordination compounds of CoII, CuII, ZnII and CdII with tioconazole (tcnz) have been synthesized and fully characterized by different techniques such as IR, UV–Vis–NIR, elemental analysis, molar conductivity, magnetic susceptibility and X-ray diffraction for the halide complexes. Different coordination geometries were stabilized by the metal ions in the obtained compounds. In all complexes the ligand is coordinated to the metal ions by the imidazolic nitrogen atom. The chloro and bromo [M(tcnz)2X2] compounds of CoII, ZnII, CuII and CdII presented a tetrahedral geometry with two ligands and two halides in the coordination sphere. In the CuII compounds with four ligands, [Cu(tcnz)4X2], a trans-octahedral geometry was acquired with the halides in axial positions. For the CuII and ZnII nitrato compounds [M(tcnz)2(NO3)2], a bidentate coordination mode of the nitrato groups stabilized a distorted cis-octahedral geometry, while in the pentacoordinated. [Cd(tcnz)3(NO3)2] compound a monodentate coordination was proposed. Additionally a binuclear [Cu2(tcnz)4(OAc)2) complex was obtained. In vitro cell growth inhibition on HCT-15 (colon), HeLa (cervix-uterine) and MCF-7 (breast) of the coordination compounds, as well for the free ligand, was investigated. Upon coordination, the IC50 value of the transition-metal compounds was improved compared to that of the free ligand. The copper(II) choro compounds showed the best cytotoxic activities on the HCT-15 cell line, being the most promising candidates for further in vitro and in vivo studies.

Coordination compounds with cobalt(II), nickel(II), copper(II) and zinc(II) and the ligand 2,6-bis(2,6-diethylphenyliminomethyl)pyridine (L) were synthesized and fully characterized by IR and UV-Vis-NIR spectroscopy, elemental analysis, magnetic susceptibility and X-ray diffraction for two representative cases. These novel compounds were designed to study their activity as anti-proliferative drugs against different human cancer cell lines. The tridentate ligand forms heptacoordinated compounds from nitrate metallic salts, where the nitrate acts in a chelating form to complete the seven coordination positions. In vitro cell growth inhibition was measured for Co(II), Cu(II) and Zn(II) complexes, as well as for the free ligand. Upon coordination, the IC50 value of the transition-metal compounds is improved compared to the free ligand. The copper(II) and zinc(II) compounds are the most promising candidates for further in vitro and in vivo studies. The activity against colon and prostate cell lines merits further research, in views of the limited therapeutic options for such cancer types.

In this work we report the synthesis and spectroscopic characterization of twenty new pentacoordinated diorganotin(IV) compounds. These compounds have been prepared in good yields by multicomponent reactions (MCRs) of α-amino acids (isoleucine, leucine, methionine, phenylalanine and aminophenylacetic acid), 2,4-dihydroxybenzaldehyde, 2-hydroxy-4-methoxybenzaldehyde and either di-n-butyltin(IV) oxide or diphenyltin(IV) oxide. All compounds were characterized by IR spectroscopy, 1H, 119Sn and 13C NMR spectroscopy and mass spectrometry. Each compound has a coordinative N→Sn bond and shows the expected 119Sn NMR chemical shift indicative of a pentacoordinated or hexacoordinated tin atom in CDCl3 and DMSO-d6, respectively. These compounds were also tested in tumoral cell lines, HeLa, HCT-15 and MCF-7, in order to evaluate the antiproliferative activity and to obtain the medial inhibitory concentrations (IC50) values.

Herein we present the synthesis, structural and spectroscopic characterization of coordination compounds of cobalt(II), copper(II) and zinc(II) with 2-methylbenzimidazole (2mbz), 2-phenylbenzimidazole (2phbz), 2-chlorobenzimidazole (2cbz), 2-benzimidazolecarbamate (2cmbz) and 2-guanidinobenzimidazole (2gbz). Their cytotoxic activity was evaluated using human cancer cell lines, PC3 (prostate), MCF-7 (breast), HCT-15 (colon), HeLa (cervic-uterine), SKLU-1 (lung) and U373 (glioblastoma), showing that the zinc(II) and copper(II) compounds [Zn(2mbz) 2 Cl 2 ]·0.5H 2 O, [Zn(2cmbz) 2 Cl 2 ]·EtOH, [Cu(2cmbz)Br 2 ]·0.7H 2 O and [Cu(2gbz)Br 2 ] had significant cytotoxic activity. The isostructural cobalt(II) complexes showed not significant activity. The cytotoxic activity is related to the presence of halides in the coordination sphere of the metal ion. Recuperation experiments with HeLa cells, showed that the cells recuperated after removing the copper(II) compounds and, on the contrary, the cells treated with the zinc(II) compounds did not. These results indicate that the mode of action of the coordination compounds is different.

The molecular interactions of 5,6-dichloro-2-(trifluoromethyl)-1H-benzimidazole (G2), an antiprotozoa with poor aqueous solubility, with 2-hydroxypropyl-α-cyclodextrin (HPαCD), methyl-β-cyclodextrin (MβCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) were examined. The aqueous solubility enhancement by cyclodextrins (CDs) was evidenced in phase-solubility diagrams, and the stoichiometry of G2/CD systems was determined by Job's plots. Two-dimensional NMR spectroscopic data revealed that a different mode of interaction took place between G2 and CDs in solution. With HPαCD, a non-inclusion complex was generated. In the case of MβCD, a typical host–guest system was obtained and with HPβCD a partial inclusion complex through the narrow side of the macrocycle was formed. ESI-mass spectrometric data confirmed the stoichiometry and mode of interaction of these systems in solution. Solid-state characterization (scanning calorimetry and powder X-ray diffraction) supported the inclusion complex formation. The leishmanicidal activity, trypanocidal activity and non-toxic profile of G2/MβCD showed the advantages of using this inclusion complex to promote the biological assays extension of G2.