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Novel complexes of type [Cu(N-N)(dmtp) 2 (OH 2 )](ClO 4 ) 2 ·dmtp (( 1 ) N-N: 2,2'-bipyridine; ( 2 ) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5- a ]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex ( 1 ) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex ( 2 ) proved to be a more potent antimicrobial in comparison with ( 1 ), but both compounds were more active in comparison with dmtp-both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide.

  In an effort to improve the antimicrobial activity of norfloxacin, a series of hybrid norfloxacin-thiazolidinedione molecules were synthesized and screened for their direct antimicrobial activity and their anti-biofilm properties. The new hybrids were intended to have a new binding mode to DNA gyrase, that will allow for a more potent antibacterial effect, and for activity against current quinolone-resistant bacterial strains. Moreover, the thiazolidinedione moiety aimed to include additional anti-pathogenicity by preventing biofilm formation. The resulting compounds showed promising direct activity against Gram-negative strains, and anti-biofilm activity against Gram-positive strains. Docking studies and ADMET were also used in order to explain the biological properties and revealed some potential advantages over the parent molecule norfloxacin., Competing Interests: The authors declare no conflict of interest.

Five new copper(II) acrylate complexes (acr is the acrylate anion: C₃H₃O₂) with imidazole derivatives (2-methylimidazole/2-MeIm, 5-methylimidazole/5-MeIm, 2-ethylimidazole/2-EtIm) of type: cis -[Cu(2-RIm)₂(acr)₂]·xH₂O (( 1 ): R = ⁻CH₃, x = 2; ( 4 ): R = ⁻CH₂⁻CH₃, x = 0), trans -[Cu(2-RIm)₂(acr)₂] (( 2 ): R = ⁻CH₃; ( 5 ): R = ⁻CH₂⁻CH₃) and trans -[Cu(5-RIm)₂(acr)₂] (( 3 ): R = ⁻CH₃) have been prepared and characterized by elemental analysis, Fourier Transform Infrared spectrometry (FTIR), Electron Paramagnetic Resonance (EPR), electronic reflectance spectroscopy, scanning electron microscopy, and mass spectrometry. The single crystal X-ray diffraction study of complexes ( 2 ) and ( 5 ) reveals that the copper(II) ion is located on an inversion center and show elongated octahedral geometry completed by two coplanar bidentate acrylates and two unidentate imidazole derivatives displayed in trans positions. For complex ( 4 ) the single crystal X-ray diffraction shows that the copper(II) ion is in a distorted octahedral environment which can be easily confused with a trigonal prism completed by two bidentate acrylates and two unidentate imidazole derivatives displayed in cis positions. These results indicate the fact that complexes ( 4 ) and ( 5 ) are the geometric isomers of the same compound bis(acrylate)-bis(2-ethylimidazole)-copper(II). Complexes ( 1 ) and ( 2 ), as well as ( 4 ) and ( 5 ), were produced simultaneously in the reaction of the corresponding copper(II) acrylate with imidazole derivatives in methanol solution. Furthermore, in order to be able to formulate potential applications of the obtained compounds, our next goal was to investigate the in vitro antimicrobial activity of the synthesized complexes against Gram-positive and Gram-negative bacteria, as well as fungal strains, of both clinical and ecological importance (biodeterioration of historical buildings). The trans isomers ( 2 ) and ( 5 ), followed by ( 4 ) have shown the broadest range of antimicrobial activity. In case of ( 1 ) and ( 2 ) isomers, the trans isomer ( 2 ) was significantly more active than cis ( 1 ), while the cis isomer ( 4 ) proved to be more active than trans ( 5 ). Taken together, the biological evaluation results indicate that the trans ( 2 ) was the most active complex, demonstrating its potential for the development of novel antimicrobial agents, with potential applications in the biomedical and restoration of architectural monuments fields.

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C. albicans is the most frequently occurring fungal pathogen, and is becoming an increasing public health problem, especially in the context of increased microbial resistance. This opportunistic pathogen is characterized by a versatility explained mainly by its ability to form complex biofilm structures that lead to enhanced virulence and antibiotic resistance. In this context, a review of the known C. albicans biofilm formation inhibitors were performed and a new N-(oxazolylmethyl)-thiazolidinedione scaffold was constructed. 16 new compounds were synthesized and characterized in order to confirm their proposed structures. A general antimicrobial screening against Gram-positive and Gram-negative bacteria, as well as fungi, was performed and revealed that the compounds do not have direct antimicrobial activity. The anti-biofilm activity evaluation confirmed the compounds act as selective inhibitors of C. albicans biofilm formation. In an effort to substantiate this biologic profile, we used in silico investigations which suggest that the compounds could act by binding, and thus obstructing the functions of, the C. albicans Als surface proteins, especially Als1, Als3, Als5 and Als6. Considering the well documented role of Als1 and Als3 in biofilm formation, our new class of compounds that target these proteins could represent a new approach in C. albicans infection prevention and management. [ABSTRACT FROM AUTHOR]