Functionalization of the A ring of pyridoacridine as a route toward greater structural diversity. Synthesis of an octacyclic analogue of eilatin.
In an effort to increase the structural diversity of pyrido[4,3,2-kl]acridines, compounds containing amino substituents on the A ring were synthesized. The key-reactions involve regioselective electrophilic aromatic substitutions. The methodology was applied to the synthesis of the extended angular octacycle 8, which conjugates the physicochemical and spectroscopic properties of the pyridoacridine skeleton with the ability of [1,10]phenanthroline ring for metal complexation. The 9-aminopyridoacridine 4 displays significant cytostatic activities against two cancer cell lines, and may be considered as a new lead in the search of active derivatives.
Bouffier
Laurent
L
Département de Chimie Moléculaire, UMR-5250 & ICMG FR-2607, CNRS-Université Joseph Fourier, 38041 Grenoble Cedex 9, France.
Dinica
Rodica
R
Debray
Julien
J
Dumy
Pascal
P
Demeunynck
Martine
M
D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry*; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism
D000166:Acridines; D054697:Cytostatic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D010618:Phenanthrolines; C475900:pyridoacridine; C097538:eilatine