title: Benzo[b]-1,8-naphthyridine derivatives: synthesis and reversal activity on multidrug resistance.
abstract: A series of benzo[b]-1,8-naphthyridine derivatives branched with various side-chains and substituents were prepared with the aim of being investigated as multidrug resistance (MDR) modulators. The syntheses were achieved from 2-halonicotinic acid and suitable aryl-amines according to a three-step procedure. All the derivatives were tested in vitro on mouse T-Lymphoma cell line L5178 transfected by MDR1 gene and the chemosensitizing properties of the compounds were compared to those of verapamil and propranolol, as well as to several other tricyclic derivatives like phenothiazines and acridines. Most of the compounds tested reversed the MDR of tumour cells more effectively than the reference drugs did and they showed more potent chemosensitizing activity than phenothiazine and acridine derivatives have.
authors.affiliation: GERCTOP/UMR CNRS 6009, Faculté de Pharmacie, Marseille, France.
authors.forename: Houria
authors.initials: H
authors.lastname: Misbahi
authors.forename: Pierre
authors.initials: P
authors.lastname: Brouant
authors.forename: Aniko
authors.initials: A
authors.lastname: Hevér
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Molnár
authors.forename: Krysztina
authors.initials: K
authors.lastname: Wolfard
authors.forename: Grabriela
authors.initials: G
authors.lastname: Spengler
authors.forename: Hafid
authors.initials: H
authors.lastname: Mefetah
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnár
authors.forename: Jacques
authors.initials: J
authors.lastname: Barbe
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D018432:Drug Resistance, Multiple / Q000235:genetics / Q000502:physiology*; D007940:Leukemia L5178 / Q000473:pathology; D051379:Mice; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009287:Naphthyridines