Novel Insight in Structure−Activity Relationship and Bioanalysis of P-Glycoprotein Targeting Highly Potent Tetrakishydroxymethyl Substituted 3,9-Diazatetraasteranes

Novel 3,9-diazatetraasteranes have been synthesized with varied aromatic substitution patterns and evaluated as P-glycoprotein (P-gp) inhibitors. Structure−activity relationships (SAR) are discussed in relation to determined physicochemical properties. The potential to induce P-gp expression has been evaluated in cancer cell lines. The bioanalytical results indicate favorable noninducing properties compared to P-gp inducing drug standard.