Antitumor Activity of Ionic Liquids Based on Ampicillin

Abstract

Significant antiproliferative effects against various tumor cell lines were observed with novel ampicillin salts as ionic liquids. The combination of anionic ampicillin with appropriate ammonium, imidazolium, phosphonium, and pyridinium cations yielded active pharmaceutical ingredient ionic liquids (API-ILs) that show potent antiproliferative activities against five different human cancer cell lines: T47D (breast), PC3 (prostate), HepG2 (liver), MG63 (osteosarcoma), and RKO (colon). Some API-ILs showed IC50 values between 5 and 42 nM, activities that stand in dramatic contrast to the negligible cytotoxic activity level shown by the ampicillin sodium salt. Moreover, very low cytotoxicity against two primary cell lines-skin (SF) and gingival fibroblasts (GF)-indicates that the majority of these API-ILs are nontoxic to normal human cell lines. The most promising combination of antitumor activity and low toxicity toward healthy cells was observed for the 1-hydroxyethyl-3-methylimidazolium-ampicillin pair ([C2 OHMIM][Amp]), making this the most suitable lead API-IL for future studies.

The Anticancer Potential of Ionic Liquids

“…There are some doubts in the IL field about the advantages and possibility of using an ion with biological activity for drug application. The important question of the toxicity of ILs has been the main reason behind the delayed entry of these compounds into biological applications . At present, there are some published reports about the development of APIs as ionic liquids and not as crystalline materials …”

“…Furthermore, the same ILs showed very low cytotoxicity against two primary cell lines of skin (SF) and gingival fibroblasts (GF), which showed that these compounds are not toxic to human cell lines at the concentration range tested (Table ). This facet of the study is of particular interest, and presents a different point of view from the majority of previously published reports, with the exception of the study reported by Kaushik and co‐workers .…”

“… Examples of potential antitumor agents in the form of ampicilin salts (adapted from Ref. with modifications).…”

“…These days the pharmaceutical industry is facing many problems and challenges in the discovery of innovative and effective drugs and their subsequent therapeutic applications . Roughly 50 % of available drugs are administered as salts, which can have many disadvantages, some of which being related to the polymorphism of drugs (i.e., the tendency of a compound to undergo structural transformations between distinct crystalline forms) .…”

“…Cancer has a significant impact on worldwide health, and this pathology requires innovative therapies that can minimize or eliminate the side effects currently associated with conventional therapies . ILs are a promising compound class in the development of new antitumor agents, as their properties are rather easily adjusted .…”