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.
Coburger
Claudius
C
Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle, Germany.
Wollmann
Jörg
J
Baumert
Christiane
C
Krug
Martin
M
Molnár
Josef
J
Lage
Hermann
H
Hilgeroth
Andreas
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D001372:Aza Compounds / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002855:Chromatography, Thin Layer; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001372:Aza Compounds