A Novel Adamantane-Derived Sulfur-Containing Schiff Base: Synthesis and Preliminary Biological Studies

Sulfur-containing compounds are an underexplored class of molecules in bioinorganic chemistry, with most works of research focused on nitrogen and oxygen-containing molecules. The presence of sulfur in drugs is promising because of its larger atomic volume, lower electronegativity and higher polarizability, which allows it to interact in unique ways with biomolecules and affect specific cell processes. Molecules containing both sulfur and nitrogen are highly versatile and particularly attractive due to the presence of hard and soft donors, enabling the coordination to a wide variety of metal centers in diverse binding modes. Recent studies depict stable S,N-coordinated metal complexes with interesting anticancer properties. In this work, we describe the synthesis and preliminary in vitro studies of an adamantane-derived Schiff Base containing nitrogen and sulfur with potential antitumor properties. Schiff Bases are prepared from the condensation between a carbonylic compound and an amine. Here, the amine in question was amantadine, which belongs to the class of aminoadamantanes. These compounds have rigid cage-shaped structures that promote drug stability and their further distribution in drug plasma, by shielding adjacent functional groups from metabolic cleavage. Aminoadamantane Schiff bases are particularly envisaged for drug development, with reported activities over some types of tumor, and biological activities have been linked to their interaction with biomolecules such as DNA, peptides and enzymes. The Schiff base of interest was prepared from the reaction between amantadine and 2-tiophencarboxaldexyde in methanol, conducted under reflux for 3 hours, leading to the formation of a white precipitate. The solid was washed with distilled water and dried in a desiccator over P2O5. Yield 59%. Elemental analysis led to the molecular formula C15H19NS. Preliminary studies were carried out to assess the cytotoxicity of the compounds. In this assay, Vero E6 cells (kidney tissue derived from a normal, adult African green monkey) were treated with the Schiff base at the concentrations of 50, 10 and 2 µM. Then, cell viability was assessed by MTT assay 72h later. DMSO was used as untreated control. Analyzing the effects on viability, we found that cell viability was 98.5% after treatment with the Schiff base even at the highest concentration. As the preliminary in vitro studies indicate that this compound is not toxic for normal cells, further biologic studies with the novel Schiff base are envisaged to evaluate its activity over cancer cells.