Synthesis and antiproliferative properties of N3/8-disubstituted 3,8-diazabicyclo[3.2.1]octane analogues of 3,8-bis[2-(3,4,5-trimethoxyphenyl)pyridin-4-yl]methyl-piperazine.
A series of novel N(3/8)-disubstituted-3,8-diazabicyclo[3.2.1]octanes in order to improve the in vitro activity of the prototype 3,8-bis[2-(3,4,5-trimethoxyphenyl)pyridyl-4-yl)methylpiperazine (1) were synthesized and evaluated by assays of growth inhibition against several tumor cell lines. Compounds 2a,b,f and m demonstrated not only growth-inhibitory activities against leukemia cancer cells, but also fairly good activities against the growth of certain solid tumors. Among them, 2a is the most potent one with IC(50) values in the low micromolar range. Moreover, compound 2a has been selected for in vitro testing on MCF-7 cell to evaluate the mode of action of this lead compound.
Filosa
Rosanna
R
Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via ponte don Melillo, 84084 Fisciano (SA), Italy. rfilosa@unisa.it
Peduto
Antonella
A
de Caprariis
Paolo
P
Saturnino
Carmela
C
Festa
Michela
M
Petrella
Antonello
A
Pau
Amedeo
A
Pinna
Gérard Aimé
GA
La Colla
Paolo
P
Busonera
Bernardetta
B
Loddo
Roberta
R
D000478:Alkylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D004396:Coloring Agents; D004171:Diploidy; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007202:Indicators and Reagents; D008872:Microwaves; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011419:Propidium; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C519544:3,8-bis(2-(3,4,5-trimethoxyphenyl)pyridin-4-yl)methyl-piperazine; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004396:Coloring Agents; D007202:Indicators and Reagents; D010879:Piperazines; D011725:Pyridines; D011419:Propidium