Differential Immunomodulatory Activities of Schiff Base Complexes Depending on their Metal Conjugation

Immunomodulatory compounds have become crucial with advances in immunotherapy. Using our own immune system cells, we can direct the immune cell function and develop desired response against a certain threat. Immunotherapy applications have been suggested against tumors, autoimmune disorders, and infectious diseases. Vaccination can be considered as one of the best known example of immunotherapy. Infectious agent's signature molecular structures are introduced to the immune cells together with the adjuvants that further activate the immune cells to mount a proper immune response and memory. Immunotherapy and vaccine formulations are in constant need of a library of immunomodulatory reagents that can be applied depending on the target. In order to expand the number of immunomodulatory reagents that can find medicinal applications, our group has been testing unique chemical structures on the immune system cells, especially macrophages. Schiff base complexes are known for their anti-inflammatory and antimicrobial activities. In this study, we used previously characterized Schiff base complexes with different metal conjugations. These molecules had differential immunostimulatory and immunomodulatory potentials on macrophages in vitro depending on the type of the conjugated metal. After light exposure, these complexes changed their characteristics and became powerful anti-inflammatory complexes. Due to their possible antimicrobial potentials, we also tested their activities against gram negative and gram positive bacteria. All of the complexes exerted antimicrobial activities which were not light responsive. Here, we present Schiff base complexes with differential immunostimulatory and immunomodulatory activities that can also efficiently eliminate gram positive and gram negative bacteria. Upon photo activation, they block the production of inflammatory TNFα cytokine. Therefore, together with the light, they can be used to treat bacterial infections associated with damaging inflammation. Graphical Abstract.