γ-Lactones α,β- and β,γ-fused to carbocycles as novel antiproliferative drugs

• Published in: Bioorganic & medicinal chemistry letters 2008-10, Vol.18 (19), p.5171-5173
• Main Authors: León, Leticia G., Machín, Rubén P., Rodríguez, Carmen M., Ravelo, José L., Martín, Víctor S., Padrón, José M.
• Format: Article
• Language: English
• Subjects: Anticancer drugs; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Combinatorial Chemistry Techniques; Drug Design; Drug discovery; Drug Screening Assays, Antitumor; Female; General aspects; Humans; Lactones - chemical synthesis; Lactones - chemistry; Lactones - pharmacology; Medical sciences; Molecular Structure; Pharmacology. Drug treatments; Privileged structures; Ring closing metathesis; Stereoisomerism; Structure-Activity Relationship; γ-Lactones
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2008.08.098

The synthesis and antiproliferative activity of γ-lactones α,β-fused and β,γ-fused to carbocycles are reported. A set of γ-lactones α,β-fused and β,γ-fused to carbocycles have been synthesized and evaluated for their in vitro antiproliferative activities using the human cancer cell lines SW1573 (lung), T-47D (breast) and WiDr (colon). The compounds are obtained by intramolecular ring closing metathesis of the corresponding dienes. Active compounds exhibited GI 50 values in the range 8–18 μM. A structure–activity relationship is also discussed.