Irina Zarafu

Synthesis and biological activities of some new isonicotinic acid 2-(2-hydroxy-8-substituted-tricyclo[7.3.1.02.7]tridec-13-ylidene)-hydrazides

A series of several new isoniazid derivatives, isonicotinic acid 2-(2-hydroxy-8-substituted-tricyclo[7.3.1.0(2.7)]tridec-13-ylidene)-hydrazides, were synthesized and fully characterized. These new isoniazid derivatives were studied regarding their antibacterial activity and cytotoxicity, as well as their influences on some metabolizing enzymes. The best anti-mycobacterial activity was observed in the case of compounds containing alkyl side chains in the 8 position of tricyclo[7.3.1.0(2.7)]tridec-13-ylidene group. On contrary, the antimicrobial activity of these new compounds against various non-tuberculosis strains showed the best activity to be with the phenyl side chain of compound 6. It proved also to be the most toxic, inducing apoptosis and blocking the cell cycle in G0/G1 phase. The cell cycle was blocked in G0/G1 phase also by compound 3, but this compound did not show any toxicity. All compounds induced the expression of NAT1 and NAT2 genes in HT-29 cell line, and the expression of CYP1A1 in HT-29 and HCT-8 cell lines. The expression level of CYP3A4 was increased by compounds 1, 6 and 7 in HCT-8 cells. These results indicated that the activation of other metabolizing pathways, apart from those of isoniazid, take place. It might also point out the possibility of an increased isoniazid acetylation ratio by co-administration with new compounds in slow acetylators.

Chemical and biological evaluation of some new antipyrine derivatives with particular properties.

Starting from 4-amino-antipyrine, six new compounds were synthesized and characterized. The new compounds contain moieties with particular properties, such are ionophore (benzo-15-crown-5), fluorescent (nitrobenzofurazan), stable free radical (nitroxide), or other types of biological active residues, like nitroderivatives, antipyrine or isoniazid residues. They were fully characterized by appropriate means ((1)H and (13)C NMR, IR, UV-Vis, fluorescence, EPR, elemental analysis) and some of their biological properties were evaluated. Hydrophobicity (R(M0), log P), total antioxidant capacity (TAC), and antimicrobial properties are also presented and discussed.

Spectral, magnetic, thermal and biological studies on Ca(II) and Cu(II) complexes with a novel crowned Schiff base

A series of complexes [Ca(HL)(OH2)4]Cl2·4H2O (1), [CuL2]·2H2O (2) and [Cu{Ca(L)(OH2)2}2]Cl4·H2O (3) (HL: 2-hydroxy-8-methyl-tricyclo[7.3.1.02.7]tridec-13-N-4′(benzo-15-crown-5-ether)-imine) were synthesised and characterised. The features of complexes have been assigned from microanalytical data, IR, UV–Vis–NIR and EPR spectra, magnetic data at room temperature as well as thermal analysis. The ligand coordinates through azomethinic nitrogen and hydroxylic oxygen at Cu(II) and through etheric oxygen at Ca(II). The electronic and EPR spectra suggest a square planar stereochemistry for Cu(II). The thermal analysis evidenced that thermal transformations are complex processes according to DTG and DTA curves including (crystallisation or coordination) water elimination, thermolyses and oxidative degradation of Schiff base. The results of the biological assays revealed that the complexes exhibited good antimicrobial activity against planktonic and sessile bacterial and fungal strains.

Lipoic Acid Gold Nanoparticles Functionalized with Organic Compounds as Bioactive Materials

Water soluble gold nanoparticles protected by lipoic acid were obtained and further functionalized by standard coupling reaction with 1-naphtylamine, 4-aminoantipyrine, and 4′-aminobenzo-15-crown-5 ether. Derivatives of lipoic acid with 1-naphtylamine, 4-aminoantipyrine, and 4′-aminobenzo-15-crown-5 ether were also obtained and characterized. All these were tested for their antimicrobial activity, as well as for their influence on mammalian cell viability and cellular cycle. In all cases a decreased antimicrobial activity of the obtained bioactive nanoparticles was observed as compared with the organic compounds, proving that a possible inactivation of the bioactive groups could occur during functionalization. However, both the gold nanoparticles as well as the functionalized bioactive nanosystems proved to be biocompatible at concentrations lower than 50 µg/mL, as revealed by the cellular viability and cell cycle assay, demonstrating their potential for the development of novel antimicrobial agents.

Antimicrobial Features of Organic Functionalized Graphene-Oxide with Selected Amines

(1) Background: Graphene oxide is a new carbon-based material that contains functional groups (carboxyl, hydroxyl, carbonyl, epoxy) and therefore can be easily functionalized with organic compounds of interest, yielding hybrid materials with important properties and applications. (2) Methods: Graphene oxide has been obtained by a modified Hummers method and activated by thionyl chloride in order to be covalently functionalized with amines. Thus obtained hybrid materials were characterized by infrared and Raman spectroscopy, elemental analysis and scanning electron microscopy and then tested for their antimicrobial and anti-biofilm activity. (3) Results: Eight amines of interest were used to functionalize grapheme oxide and the materials thus obtained were tested against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacterial strainsin plankonic and biofilm growth state. Both amines, as well as the functionalized materials, exhibited anti-microbial features. Three to five functionalized graphene oxide materials exhibited improved inhibitory activity against planktonic strains as compared with the respective amines. In exchange, the amines alone proved generally more efficient against biofilm-embedded cells. (4) Conclusions: Such hybrid materials may have a wide range of potential use in biomedical applications.

Thermal, spectral and biological characterisation of copper(II) complexes with isoniazid-based hydrazones

A series of complexes [Cu(L)(CH3COO)2]·nH2O (L: isonicotinic acid 2-(2-hydroxy-8-substituted-tricyclo[7.3.1.02.7]tridec-13-ylidene)-hydrazones) were synthesised and characterised. The features of complexes have been assigned from microanalytical data, ESI–MS, IR, UV–Vis–NIR and EPR spectra, as well as thermal analysis. The ligands (hydrazones and acetate) act as chelate in the octahedral distorted complexes of Cu(II). The thermal analysis evidenced complex thermal transformations such as thermolises and oxidative degradation of hydrazone moiety as well as acetate into carbonate transformation, followed by carbonate decomposition up to CuO. The complexes were evaluated for their interaction with microbial and immortalised human cells, in order to formulate some potential biomedical applications, beyond the antimycobacterial activity.

Synthesis, thermal, spectral, antimicrobial and cytotoxicity profile of the Schiff bases bearing pyrazolone moiety and their Cu(II) complexes

A series of Schiff bases resulted in the [1 + 1] condensation of 8-alkyl-2-hydroxy-tricyclo[7.3.1.02.7]-tridecan-13-one with the 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one, and their complexes CuL(CH3COO)2·nH2O were synthesized. The compounds were characterized by microanalytical, ESI–MS, NMR, IR, electronic and EPR spectra. Based on the ESI–MS and IR spectra, a mononuclear structure with both Schiff base and acetate as chelate was proposed for complexes. An elongated rhombic stereochemistry was assigned considering electronic and EPR data. The thermal analyses have evidenced processes as water elimination, acetate decomposition as well as oxidative degradation of the Schiff base moiety. The bioevaluation of compounds in relation to planktonic and biofilm-embedded microbial cells, as well as to human cells, indicates an improved activity of complexes over ligands. The same tendency was observed for antioxidant activity.

EPR Spectra of a Mono- and a Hetero-Diradical in Nematic and Isotropic Phases

A hybrid hydrazine–nitroxide monoradical and the corresponding heterohydrazyl– nitroxide diradical were used as probes in 4-cyano-4′-pentylbiphenyl liquid crystal. EPR data (hyperfine constants, rotational time, and anisotropy parameter values) are reported in the range of 25°C–55°C. It was shown by EPR spectrometry that the nitroxide moiety gives an anisotropic triplet line, while the hydrazyl moiety cannot be detected under these conditions.