In the recent years, the emergence of resistance and multiresistance to antimicrobial substances has led to increasing concerns and interests in finding new antimicrobial agents and identifying new strategies for the treatment of infectious diseases [1–4]. Thiourea derivatives possess many biological activities, including antimicrobial activity, having interesting applications in numerous fields (in agriculture, as ligands useful in coordination chemistry, in analytical chemistry, in anion recognition, and in catalysis).
The synthesis and antibacterial activity of thiourea derivatives has been the subject of numerous investigations. Some new substituted 1,3,5-triazine with 1,2,4-triazole and substituted thiourea and urea were previously synthesized and evaluated for their in vitro inhibitory activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans, some of them showing excellent antimicrobial activity .
Sarmah and coworkers synthesized and characterized new compounds using the substitution of chlorine in cyanuric chloride by some moieties with biological importance, such as substituted thiourea and heterocyclic systems, in order to achieve enhanced antimicrobial activity against different bacterial and fungal strains, favored by the presence of electron-withdrawing groups on the aromatic ring as compared to compounds with electron-donating groups . The (E)-N-[4-(benzamidomethyleneamino)phenylcarbamothioyl]benzamide synthesized by Kurt et al. exhibited in vitro antibacterial activity against B. subtilis.
The biological significance of thioureas and 2-aminobenzothiazoles stimulated research to investigate the synergistic effects of these moieties to afford the design of a new class of heterocyclic thioureas. The new 1-aroyl-3-(substituted-2-benzothiazolyl)-thioureas were found to exhibit moderate to potent activity towards S. aureus, B subtilis, P. aeruginosa, and E. coli, as compared to the standard drugs . Some compounds of the novel series of benzothiazolyl thiourea derivatives were equipotent with ampicillin against S. aureus and E. coli and showed good activity against Mycobacterium tuberculosis H37Rv. Also, they were evaluated for in vitro cytotoxicity against MCF-7 breast cancer cells .
N-phenyl- and N-benzoylthiourea derivatives obtained by a simple and inexpensive manner display selective antimicrobial activities against Cladosporium cladosporioides, B. subtilis, and Micrococcus luteus. Benzoylthioureas were more active than the corresponding phenyl ones .
5-Thiourea oxazolidinones were synthesized and their antibacterial activity against Gram-positive bacteria including methicillin-resistant S. aureus and vancomycin-resistant Enterococcus was evaluated. This activity was significantly affected by the compounds' lipophilicity, especially the calculated log p value .
Medical device-related infections account for a substantial morbidity, causing an important economic burden by the increase of antibiotic treatment and hospitalization days, as well as the health-care-associated costs [12–14]. The topological and chemical characteristics of the medical device surface are influencing microbial adherence, the less likely to be colonized being the perfectly smooth, hydrophilic ones. A lot of strategies have been employed to prevent medical device-related infections, one of them being surface modification to prevent microbial population and biofilm formation by (1) the chemical modification of the surface with protein, (2) the modification of the surface with quaternary ammonium salts acting as bacteria-repellent coatings, (3) the incorporation and release of antibiotics from the surface, and (4) the use of noble metals and especially silver on the surface as antimicrobial coatings .
There are a lot of reports on the antimicrobial and anti-biofilm properties of different types of nanoparticles, especially metals or metallic oxide-containing ones (silver, copper, gold, and ZnO) [16–26], as well as core/shell nanosystems (e.g., CoFe2O4/oleic acid, Fe3O4/oleic acid, and Fe3O4/PEG600) [27–31] that could be manipulated and improved, potentially providing a new method for treating antibiotic-resistant device-related infections [32–35]. In the last year, two articles were published opening a new perspective for obtaining new antimicrobial and anti-biofilm surfaces, based on hybrid functionalized nanostructured biomaterials [36, 37]. The first one showed that the Rosmarinus officinalis essential oil-coated Fe3O4/C18 strongly inhibited the adherence ability and biofilm development of the C. albicans and Candida tropicalis tested strains to the catheter surface, and the second showed that the usnic acid-coated Fe3O4/C18 strongly inhibited the adherence ability and biofilm development of the S. aureus tested strain to the coverslip surface, as shown by viable cell counts (VCCs) and confocal laser scanning microscopy. These material-based approaches to the control of fungal/microbial adherence could provide both (1) new tools to study mechanisms of fungal/microbial virulence and biofilm formation and (2) approaches to the design of film-coated surfaces or to treat the surfaces of solid and fiber-based materials that prevent or disrupt the formation of fungal/microbial biofilms.
Taking into consideration the aforementioned significant antimicrobial activity of thioureas, in order to continue our work on the evaluation of the bioactivity of compounds with thiourea moiety, we decided to design a new nanosystem combining new 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl)-benzamides and a Fe3O4/C12 core/shell nanostructure with up to 5-nm size for catheter surface coating, with an improved resistance to S. aureus ATCC 25923 and P. aeruginosa ATCC 27853 colonization and subsequent in vitro biofilm development.