Synthesis of diphenylcarbazoles as cytotoxic DNA binding agents.
We report the synthesis of a series of novel diphenylcarbazoles designed to interact with DNA. The compounds bearing two or three dimethylaminoalkyloxy side chains were found to bind much more tightly to DNA, preferentially at AT-rich sites, than the corresponding hydroxy compounds. The DNA binding compounds exhibit potent cytotoxic activity toward P388 leukemia cells. The 3,6-diphenylcarbazole thus represent an interesting scaffold to develop antitumor agents interacting with nucleic acids.
Jacquemard
Ulrich
U
Institut de Chimie Organique et Analytique, UMR 6005, Universite d'Orleans, B.P. 6759, 45067 Orleans 2, France.
Routier
Sylvain
S
Tatibouët
Arnaud
A
Kluza
Jérôme
J
Laine
William
W
Bal
Christine
C
Bailly
Christian
C
Mérour
Jean-Yves
JY
D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D005434:Flow Cytometry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D011067:Poly dA-dT / Q000737:chemistry; D013329:Structure-Activity Relationship; D044366:Transition Temperature / Q000187:drug effects
D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D002227:Carbazoles; D006576:Heterocyclic Compounds, 4 or More Rings; D011067:Poly dA-dT; D004247:DNA