Multidrug Resistance Reversed by Maleimide Interactions. A Biological and Synthetic Overview for an Emerging Field

Multidrug Resistance (MDR) can be considered one of the most frightening adaptation types in bacteria, fungi, protozoa, and eukaryotic cells. It allows the organisms to survive the attack of many drugs used in the daily basis. This forces the development of new and more complex, highly specific drugs to fight diseases. Given the high usage of medicaments, poor variation in active chemical cores, and self-medication, the appearance of MDR is more frequent each time, and has been established as a serious medical and social problem. Over the years it has been possible the identification of several genes and proteins responsible for MDR and with that the development of blockers of them to reach MDR reversion and try to avoid a global problem. These mechanisms also have been observed in cancer cells, and several calcium channel blockers have been successful in MDR reversion, and the maleimide can be found included in them. In this review, we explore particularly the tree main proteins involved in cancer chemoresistance, MRP1 (encoded by ABCC1), BCRP (encoded by ABCG2) and P-gp (encoded by ABCB1). The participation of P-gp is remarkably important, and several aspects of its regulations are discussed. Additionally, we address the history, mechanisms, reversion efforts, and we specifically focused on the maleimide synthesis as MDR-reversers in co-administration, as well as on how their biological applications are imperative to expand the available information and explore a very plausible MDR reversion source.