The transmembrane protein family known as aquaporins selectively allows the passage of water through the plasma membrane. 13 mammalian aquaporins have been identified so far. They are distributed throughout the body, and play an important role in maintaining water homeostasis in living cells. For that reason aquaporin modulators provide new therapeutical options for treatment of many disorders associated with water imbalance. In brain AQP4 is the most abundantly expressed aquaporin and is widely distributed. Cerebral edema leads to increased mortality and morbidity. In cytotoxic brain edema, AQP4 levels are up-regulated. Therefore, aquaporin-4 inhibitors would provide a new therapeutical option to reduce brain edema in several cerebral disorders. A short review of the discovery of aquaporins, their distribution and function in mammalian cells has been presented.
In this project, we synthetized lipophilic derivatives with potential AQP4 inhibitory effect. Synthesized compounds remain to be tested biologically.