title: Fujita-Ban QSAR analysis and CoMFA study of quinoline antagonists of immunostimulatory CpG-oligodeoxynucleotides.
abstract: One hundred seven 2-arylquinolin-4-amines were assayed in vitro for inhibition of the immunostimulatory effect of oligodeoxynucleotides containing a CpG-motif. The compounds are functionalized with various basic and non-basic groups at the aryl moiety and at the amino substituent of the quinolin-4-amine, and some of them contain an additional substituent at position 6 or 7 of the quinoline. Activities of these antagonists, expressed as EC(50) values, range from 0.2 to 200nM. A statistically significant structure-activity correlation was obtained for the Fujita-Ban variant of the classical Free-Wilson analysis. The CoMFA results derived from several models consistently indicate that electrostatic interactions of the molecules with a biological receptor contribute to biological activities to a greater extent than steric effects.
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Paliakov
authors.forename: Maged
authors.initials: M
authors.lastname: Henary
authors.forename: Martial
authors.initials: M
authors.lastname: Say
authors.forename: Steven E
authors.initials: SE
authors.lastname: Patterson
authors.forename: Alesia
authors.initials: A
authors.lastname: Parker
authors.forename: Lori
authors.initials: L
authors.lastname: Manzel
authors.forename: Donald E
authors.initials: DE
authors.lastname: Macfarlane
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: Lucjan
authors.initials: L
authors.lastname: Strekowski
mesh_terms: D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors*; D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004354:Drug Screening Assays, Antitumor; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides