title: Structure-activity relationship studies on benzofuran analogs of propafenone-type modulators of tumor cell multidrug resistance.
abstract: A series of benzofurylethanolamine analogs of propafenone (1a) have been prepared and evaluated for multidrug resistance-reversing activity in two in vitro assay systems. As for propafenones, an excellent correlation of biological data with calculated lipophilicity values was found for benzofurans, whereby the latter generally had lower activity/lipophilicity ratios. Almost identical slopes of the regression lines were obtained for both propafenones and benzofurans. Multiple linear regression analysis of the complete data set yielded an equation with excellent predictive power (r2 cross-valid = 0.968). Interaction measurements with artificial membranes indicated that the differences in activity between these two series of compounds are not due to differences in the interaction pattern with biological membranes.
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Vienna, Wien, Austria. ecker@speedy.pch.univie.ac.at
authors.forename: G
authors.initials: G
authors.lastname: Ecker
authors.forename: P
authors.initials: P
authors.lastname: Chiba
authors.forename: M
authors.initials: M
authors.lastname: Hitzler
authors.forename: D
authors.initials: D
authors.lastname: Schmid
authors.forename: K
authors.initials: K
authors.lastname: Visser
authors.forename: H P
authors.initials: HP
authors.lastname: Cordes
authors.forename: J
authors.initials: J
authors.lastname: Csöllei
authors.forename: J K
authors.initials: JK
authors.lastname: Seydel
authors.forename: K J
authors.initials: KJ
authors.lastname: Schaper
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D001572:Benzofurans / Q000138:chemical synthesis / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002478:Cells, Cultured; D003630:Daunorubicin / Q000633:toxicity; D018432:Drug Resistance, Multiple / Q000502:physiology*; D004983:Ethanolamines / Q000138:chemical synthesis / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D011405:Propafenone / Q000031:analogs & derivatives*; D012044:Regression Analysis; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001572:Benzofurans; D004983:Ethanolamines; D008081:Liposomes; D008567:Membranes, Artificial; D012235:Rhodamines; D020112:Rhodamine 123; D011405:Propafenone; D003630:Daunorubicin