Analogs of a 4-aminothieno[2,3-d]pyrimidine lead (QB13) as modulators of P-glycoprotein substrate specificity.
P-glycoprotein (P-gp) is an important factor in the development of multidrug resistance (MDR) in cancer cells. In literature reports, a thieno[2,3-d]pyrimidine (QB13) was described as P-gp modulator and opposed effects on the cell accumulation of distinct P-gp substrates were postulated. On the basis of this lead structure, a series of 2-alkylthio-4-aminothieno[2,3-d]pyrimidines was prepared and tested in a daunorubicin accumulation assay. Modulation of substrate specificity was shown for selected compounds in cytotoxicity (MTT) assays.
Häcker
Hans-Georg
HG
Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
de la Haye
Antje
A
Sterz
Katja
K
Schnakenburg
Gregor
G
Wiese
Michael
M
Gütschow
Michael
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000378:metabolism; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D003630:Daunorubicin / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008968:Molecular Conformation; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013379:Substrate Specificity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D011743:Pyrimidines; D011799:Quinazolines; C476003:thienopyrimidine; D003630:Daunorubicin