Benzo[b]-1,8-naphthyridine derivatives: synthesis and reversal activity on multidrug resistance.
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.
Misbahi
Houria
H
GERCTOP/UMR CNRS 6009, Faculté de Pharmacie, Marseille, France.
Brouant
Pierre
P
Hevér
Aniko
A
Molnár
Anna Maria
AM
Wolfard
Krysztina
K
Spengler
Grabriela
G
Mefetah
Hafid
H
Molnár
Joseph
J
Barbe
Jacques
J
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
D000970:Antineoplastic Agents; D009287:Naphthyridines