Synthesis of 2,6-diphenylpyrazine derivatives and their DNA binding and cytotoxic properties.
A series of 2,6-diphenylpyrazine derivatives was synthesized from 2,6-dichloropyrazine and 4-methoxyphenylboronic acid using palladium(0) as catalyst in a Suzuki methodology. After deprotection of the hydroxyl, alkylation reactions with different halides afforded compounds 5-8 bearing hydrophilic chains. DNA binding and cytotoxic properties were investigated. Compound 11 bearing imidazoline terminal groups was found to be a potent AT-specific DNA minor groove binder but there was no relationship between DNA interaction and cytotoxicity. However, in all cases the incorporation of the pyrazine ring was found to promote the cytotoxicity of the molecules compared to the corresponding pyridine analogues, previously synthesized.
Dias
Nathalie
N
Inserm U-524, Centre Oscar Lambret, IRCL, Place de Verdun, 59045 Lille, France.
Jacquemard
Ulrich
U
Baldeyrou
Brigitte
B
Lansiaux
Amélie
A
Goossens
Jean-François
JF
Bailly
Christian
C
Routier
Sylvain
S
Mérour
Jean-Yves
JY
D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000737:chemistry; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000737:chemistry
D011719:Pyrazines; D010165:Palladium; D004247:DNA; D003850:Deoxyribonuclease I