Discovery of 9,10-Dihydroacridines as Novel Class of ABCB1 Inhibitors.
Nonplanar 9,10-dihydroacridines were synthesized as promising C2 symmetric molecular scaffolds as inhibitors of the transmembrane efflux pump ABCB1. Within the series structure-activity relationships are discussed revealing the importance of hydrogen bond acceptor functions. A selectivity of ABCB1 inhibition is demonstrated for selected candidates and a bioanalytical study proved nontoxicity as well as missing ABCB1 substrate properties. The results encourage to further develop the promising class of ABCB1 inhibitors.
Andreas
A
Hilgeroth
Marc
M
Hemmer
Sebastian
S
Neuber
Josef
J
Molnár
Institute of Pharmacy, Martin- Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Germany. andreas.hilgeroth@pharmazie.uni-halle.de.
Hermann
H
Lage
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000166:Acridines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D006801:Humans; D006860:Hydrogen Bonding; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000166:Acridines; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins