Synthesis and biological evaluation of O-alkylated tropolones and related α-ketohydroxy derivatives as ribonucleotide reductase inhibitors

• Published in: European journal of medicinal chemistry 2001-06, Vol.36 (6), p.561-568
• Main Authors: Tamburlin-Thumin, Isabelle, Crozet, Michel P., Barrière, Jean-Claude, Barreau, Michel, Riou, Jean-François, Lavelle, François
• Format: Article
• Language: English
• Subjects: Animals; anticancer; Antineoplastic agents; Biological and medical sciences; Biopolymers; Brain; Cell Division - drug effects; DNA - biosynthesis; Drug Design; Drug Evaluation, Preclinical; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; General aspects; Magnetic Resonance Spectroscopy; Medical sciences; Microtubules - chemistry; Microtubules - metabolism; O-alkylated α-ketohydroxy compounds; Pharmacology. Drug treatments; phase-transfer O-alkylation; ribonucleotide reductase inhibitors; Ribonucleotide Reductases - antagonists & inhibitors; Ribonucleotide Reductases - metabolism; Structure-Activity Relationship; Swine; Tropolone - analogs & derivatives; Tropolone - chemical synthesis; Tropolone - chemistry; Tropolone - pharmacology; tropolones; Tubulin - metabolism; Tumor Cells, Cultured
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/S0223-5234(01)01249-1

A series of O-alkylated tropolones and related α-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.