Synthesis and biological evaluation of O-alkylated tropolones and related alpha-ketohydroxy derivatives as ribonucleotide reductase inhibitors.
A series of O-alkylated tropolones and related alpha-ketohydroxy compounds were evaluated for their biological activities and were shown to present an expected ribonucleotide reductase inhibition and cytotoxicity against some cancer cell lines but no antitubulin activity. Pharmacomodulation studies were realised to understand and enhance the observed activities. These original benzylic, heterocyclic and allylic compounds have been synthesised by a phase-transfer catalysed O-alkylation developed in our laboratories.
Tamburlin-Thumin
I
I
LCMO, UMR 6517, CNRS Universités d'Aix-Marseille 1 et 3, Av. Escadrille Normandie-Niemen, BP 562, F-13397 Cedex 20, Marseille, France.
Crozet
M P
MP
Barrière
J C
JC
Barreau
M
M
Riou
J F
JF
Lavelle
F
F
D000818:Animals; D001704:Biopolymers; D001921:Brain; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine; D014334:Tropolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001704:Biopolymers; D004791:Enzyme Inhibitors; D014404:Tubulin; D014334:Tropolone; D004247:DNA; D012264:Ribonucleotide Reductases