Letícia R. Teixeira

Nickel(II), Copper(I) and Copper(II) Complexes of Bidentate Heterocyclic Thiosemicarbazones

Nickel(II) and copper(I) or copper(II) complexes of thiosemicarbazones derived from 3- and 4-formylpyridine (H3FPT and H4FPT) and 3- and 4-acetylpyridine (H3APT and H4APT) have been prepared and characterized by microanalyses, molar conductivity and magnetic susceptibility measurements and by their NMR (in the case of copper(I) and diamagnetic nickel(II) complexes) and IR spectra.

Atypical fluoroquinolone gold(III) chelates as potential anticancer agents: Relevance of DNA and protein interactions for their mechanism of action

Quinolones are known for their antimicrobial and antitumor activities. Gold(III) compounds constitute an emerging class of biologically active substances, of special interest as potential anticancer agents. In this work three gold(III) complexes of the fluoroquinolones antimicrobial agents norfloxacin (NOR), levofloxacin (LEVO) and sparfloxacin (SPAR) were prepared and characterized with physicochemical and spectroscopic techniques. In these complexes, NOR, LEVO and SPAR act as bidentate neutral ligands bound to gold(III) through the nitrogen atoms of the piperazine ring, which is an unusual mode of coordination for this class of compounds. Two chloride ions occupy the remaining coordination sites. The cytotoxic activity of the fluoroquinolones and their gold(III) complexes was tested against the A20 (murine lymphoma), B16-F10 (murine melanoma) and K562 (human myeloid leukemia) tumor cell lines as well as the L919 (murine lung fibroblasts) and MCR-5 (human lung fibroblasts) normal cells lines. All complexes were more active than their corresponding free ligands. Complex [AuCl(2)(LEVO)]Cl was selected for DNA fragmentation and cell cycle analysis. Spectroscopic titration with calf-thymus DNA (CT DNA) showed that the complexes can bind weakly to CT DNA, probably by an external contact (electrostatic or groove binding). The complexes exhibit good binding propensity to bovine serum albumin (BSA) having relatively high binding constant values.

Structural and spectral studies of thiosemicarbazones derived from 3- and 4-formylpyridine and 3- and 4-acetylpyridine

Abstract Crystal structures of thiosemicarbazones prepared from 3- and 4-formylpyridine and 3- and 4-acetylpyridine are included along with their UV spectra. 4-Formylpyridine thiosemicarbazone has the following structural properties: monoclinic, P21/n, a=7.2420(5), b=13.961(1), c=8.415(1) A , β=90.90(1)°, V=850.7(1) A 3 and Z=4; for 3-formylpyridine thiosemicarbazone: monoclinic, C2/c, a=13.661(2), b=7.1120(4), c=19.046(2) A , β=107.71(1)°, V=1762.8(3) A 3 and Z=8; for 4-acetylpyridine thiosemicarbazone: triclinic, P-1, a=8.104(3), b=8.512(2), c=8.708(3) A , α=83.85(0), β=66.66(0), γ=62.87(0)°, V=488.9(3) A 3 and Z=2; for 3-acetylpyridine thiosemicarbazone monoclinic, P21/a, a=8.408(1), b=11.853(2),= c=9.777(3) A , β=97.66(2)°, V=985.7(4) A 3 and Z=4. Intramolecular and intermolecular hydrogen bonding are both present. There is a difference in the angles between the mean planes of the pyridine ring and thiosemicarbazone moiety in the two series.

Cobalt(II) and nickel(II) complexes of N(4') substituted 3- and 4-acetylpyridine thiosemicarbazones

CoII and NiII complexes of N(4′)-methyl and N(4′)-ethyl thiosemicarbazones derived from 3- and 4-acetylpyridine have been prepared and characterized by microanalyses, magnetic susceptibility and molar conductivity measurements and by their electronic, i.r. and n.m.r. (in the case of NiII complexes) spectra.

Crystal structures and IR, NMR and UV spectra of 4-formyl- and 4-acetylpyridine N(4)-methyl- and N(4)-ethylthiosemicarbazones

Abstract 4-Formyl- and 4-acetylpyridine N(4)-methyl- and N(4)-ethylthiosemicarbazone have been prepared, their structures solved and IR, NMR and UV spectra recorded. Intramolecular and intermolecular hydrogen bonding are both present, but the mode of the intermolecular interaction differs in the four compounds. Further, there is a significant difference in their angles between the mean planes of the pyridine ring and thiosemicarbazone moiety. The 1H NMR spectral studies show significant differences between the compounds as do UV and IR spectra.

An effective anticonvulsant prepared following a host–guest strategy that uses hydroxypropyl-β-cyclodextrin and benzaldehyde semicarbazone☆

The convulsions of approximately 25% of epileptics are inadequately controlled by currently available medication; therefore the preparation of new antiepileptic drugs is of great interest. Aryl semicarbazones can be considered a new class of compounds presenting anticonvulsant activity. In addition, they can be orally administered and are more active as anticonvulsants than mephenytoin or phenobarbital. However, one disadvantage of these compounds is their low water solubility. As a strategy to circumvent this problem, a 1:1 inclusion compound of benzaldehyde semicarbazone (BS) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was prepared and characterized. The anticonvulsant activities of the free semicarbazone and of the inclusion compound were evaluated in rats using the maximum electroshock and audiogenic seizures screenings. In both tests the minimum dose of compound necessary to produce activity decreases from 100mg/kg for the free semicarbazone to 35 mg/kg for the inclusion compound, indicating a significant increase in the bio-availability of the drug.

Platinum(II) complexes of 2-, 3-, and 4-formyl-pyridine thiosemicarbazone and 2-, 3- and 4-acetyl-pyridine thiosemicarbazone

Seven platinum(II) complexes isolated from thiosemicarbazones derived from 2-, 3- and 4-formylpyridine and 2-, 3-, and 4-acetylpyridine have been characterised by microanalyses, molar conductivities and by their i.r. and 1H-n.m.r. spectra.

Inclusion of Benzaldehyde Semicarbazone into β-Cyclodextrin Produces a Very Effective Anticonvulsant Formulation

Aryl semicarbazones can be considered a novel class of compounds presenting anticonvulsant activity. In order to improve the efficiency and bioavailability of benzaldehyde semicarbazone (BS) we used the host–guest strategy and β-cyclodextrin (β-CD) to prepare a BS/β-CD 1:1 inclusion compound, which was characterized by thermal analyses (TG, DTG, DSC), XRD powder pattern diffraction analyses, infrared data and 1H, 13C, 2D-ROESY NMR and 1H relaxation times. The BS/β-CD inclusion compound was tested in rats using the maximum electroshock (MES) screen. The minimum dose necessary to produce anticonvulsant activity decreased from 100 mg/Kg (ip or vo) for the free semicarbazone to 25 mg/Kg/vo (75%) and 15 mg/Kg/ip (85%), indicating that the host–guest strategy that uses β-CD and BS is very effective and could be successfully employed in the preparation of pharmaceutical formulationof anticonvulsants.

Iron(III) complexes with N 4- para -tolyl-thiosemicarbazones: spectral and electrochemical studies and toxicity to Artemia salina

Iron(III) complexes [Fe(H2Fo4pT)Cl3] (1), [Fe(H2Ac4pT)Cl3] (2) and [Fe(H2Bz4pT)Cl3] (3) with N4 -para-tolyl-thiosemicarbazones derived from 2-formyl (H2Fo4pT), 2-acetyl (H2Ac4pT) and 2-benzoylpyridine (H2Bz4pT) were prepared and characterized. EPR data for 1–3 reveal the presence of low-spin iron(III) with d xz ²d yz ²d xy ¹ ground state. Electrochemical studies of the complexes showed mostly metal-centered redox changes with a quasi-reversible Fe(III)/Fe(II) couple. H2Fo4pT and H2Ac4pT exhibited toxicity against Artemia salina at low doses (LD50 = 27.5 µM and LD50 = 4.7 µM, respectively). Upon coordination the toxicity increased substantially in the case of [Fe(H2Fo4pT)Cl3] (LD50 = 1.9 µM) and did not change for [Fe(H2Ac4pT)Cl3]. H2Bz4pT and its iron(III) complex were not soluble in water.

Norfloxacin Zn(II)-based complexes: acid base ionization constant determination, DNA and albumin binding properties and the biological effect against Trypanosoma cruzi.

Zn(II) complexes with norfloxacin (NOR) in the absence or in the presence of 1,10-phenanthroline (phen) were obtained and characterized. In both complexes, the ligand NOR was coordinated through a keto and a carboxyl oxygen. Tetrahedral and octahedral geometries were proposed for [ZnCl2(NOR)]·H2O (1) and [ZnCl2(NOR)(phen)]·2H2O (2), respectively. Since the biological activity of the chemicals depends on the pH value, pH titrations of the Zn(II) complexes were performed. UV spectroscopic studies of the interaction of the complexes with calf-thymus DNA (CT DNA) have suggested that they can bind to CT DNA with moderate affinity in an intercalative mode. The interactions between the Zn(II) complexes and bovine serum albumin (BSA) were investigated by steady-state and time-resolved fluorescence spectroscopy at pH 7.4. The experimental data showed static quenching of BSA fluorescence, indicating that both complexes bind to BSA. A modified Stern–Volmer plot for the quenching by complex 2 demonstrated preferential binding near one of the two tryptophan residues of BSA. The binding constants obtained (Kb) showed that BSA had a two orders of magnitude higher affinity for complex 2 than for 1. The results also showed that the affinity of both complexes for BSA was much higher than for DNA. This preferential interaction with protein sites could be important to their biological mechanisms of action. The analysis in vitro of the Zn(II) complexes and corresponding ligand were assayed against Trypanosoma cruzi, the causative agent of Chagas disease and the data showed that complex 2 was the most active against bloodstream trypomastigotes.