ABSTRACT Aquaporins (AQPs) constitute a family of integral membrane proteins that serve as channels for selective transport of water and, in some cases,small solutes across the cell membrane. So far, 13 members of the aquaporin family have been discovered distributed in different mammalian tissues. The flow of water across lipid bilayers is necessary for fundamental cell function. Aquaporins play an important role in regulating the water homeostasis in the diverse organs, and is heavily involved in human pathophysiology. Therefore, aquaporins may represent novel therapeutic targets in several diseases. In particular, there is a lot of interest for an aquaporin-4 inhibitor in the treatment of brain edema. In this study, we synthesized and examined the effect of 7 synthesized peptides, ranging in size from a tetrapeptide to a decapeptide, a synthesized analogue of the alleged unspecific AQP inhibitor phloretin and some commercially available compounds, such as dipolar compounds, ion channel inhibitors, sulphonamides and related compounds, on human aquaporin-4 and aquaporin from Plasmodium falciparum expressed in Xenopus laevis oocytes. The assay indicated no inhibition of hAQP4 or PfAQP a concentrations in the 0.1 - 0.3 mM range. Here we also present a short review of the functional and structural properties of aquaporins, their role in mammalian physiology and pathophysiology and their potential as therapeutic targets.