DICATIONIC IMIDAZOLIUM SALTS: TUNABLE ANTIMICROBIAL AND ANTITUMORAL CHEMIOTHERAPEUTIC LEADS

The chemical synthesis of novel chemotherapeutical leads is evolving thanks to possibility to design molecules with desired physical-chemical and, thus, biological properties. The imidazolium salts, recently proven effective to inhibit bacterial and/or cancer cell growth, posses an amphiphilic nature that is conferred by the imidazolium cation having a polar head generally coupled with aliphatic side chains. Thus, biological properties of imidazolium salts can be tuned through modifications involving the cation structure and/or the anion nature. By covalently linking two imidazolium rings, di-imidazolium salts were obtainedobtain differing in: i) kind of anions; ii) geometric isomerization of di-imidazolium anions; iii) length of the imidazolium alkyl side chains. Preliminarly, eleven di-imidazolium salts, differing for their anionic counterparts, were assayed for: i) antibacterial property, quantified as the minimal concentration inhibiting at least the 90% of bacterial growth (MIC90) using Escherichia coli and Micrococcus luteus as Gram-negative and Gram-positive tester strains; ii) antitumoral activity measured as the concentration inhibiting the 50% of cell growth (IC50) using SKBR-3 breast cancer cell line. All the assayed salts possesses biological activity showing i) 0.1-0.5 and 25-50 µg/ml as MIC90 values against of M. luteus, and E. coli; respectively, and ii) 30-55 µg/ml as IC50 values. Among the tested di-imidazolium salts, three were chosen to further investigate the relationship between biological efficacy and either length of alkyl side chains or imidazolium ring configurations. Geometric isomerization revealed few or no effect while a positive correlation between alkyl chain length and cell-growth inhibitory efficacy was shown. Although further studies have to be performed to elucidate the molecular mechanisms leading to cell growth arrest, this study provide insights on the attractive possibility of di-imidazolium salt exploitation as chemotherapeutical compounds whose activity can be tuned by modifying structural characteristics.