Multi-Drug Resistant Reversal Agents:An Overview of Structure-Activity Relationship

Multidrug resistance (MDR) against various anticancer drugs ofdifferent compound classes has maintained thecentral problem in anticancer drug therapies over the last decades. Multidrug efflux pumps of various types havebeen identified to be mainly causative agents in the multidrug affected process of MDR by transportinganticancerdrugs out of the cells.Therefore, effective intracellular drug levels are no longer reached.P-Glycoprotein,the plasma membrane protein responsible forthe multidrug resistance of some tumor cells, is an activetransporter ofa number of structurally unrelated hydrophobicdrugs.The inhibition of the efflux pump activity by drugs turned out as the most perspective approach to combat MDR.MDR reversing agents which are categorized into three classes are diverse andstructurally unrelated compounds.Knowing structure-activity relationships would help us to design more effective MDR reversing agents that areurgently needed for clinical use.In this study structure –activity relationships(SAR) of MDR reversing agents arediscussed and somesubstructural features related to MDR activity were identified. For example, the CH۲ –CH۲–N–CH۲–CH۲ group was found in most of the active compounds, and the activity was further enhanced by the presenceof (di)methoxylphenyl groups, whereas the presence of a stable quaternary ammonium salt, a carboxylic, a phenol,or an aniline group was found to be detrimental to activity.

کلیدواژه ها:

MDR ، P-Glycoprotein ، cancer ، structure-activity relationship(SAR).