Synthesis and biological evaluation of crown ether acyl derivatives

• Published in: Bioorganic & medicinal chemistry letters 2016-11, Vol.26 (22), p.5591-5593
• Main Authors: Febles, Martín, Montalvão, Sofía, Crespín, Guillermo Díaz, Norte, Manuel, Padrón, José M., Tammela, Päivi, Fernández, José J., Daranas, Antonio Hernández
• Format: Article
• Language: English
• Subjects: 18-Crown-6; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antimicrobial; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative; Candida albicans - drug effects; Candidiasis - drug therapy; Cell Line, Tumor; Cell Proliferation - drug effects; Crown ether; Crown Ethers - chemistry; Crown Ethers - pharmacology; Drug Screening Assays, Antitumor; Humans; Neoplasms - drug therapy; Staphylococcal Infections - drug therapy; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Structure–activity
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.09.066

[Display omitted] A set of crown ethyl acyl derivatives based on 18-crown-6 moiety was synthesized and evaluated for biological activity. In vitro antiproliferative profiling demonstrated significant activities against HBL-100, HeLa, SW1573 and WiDr human cell lines. The most active compound exhibited GI50 values in the range of 3.7–5.6μM. Antimicrobial evaluation showed that three polyaromatic compounds were active against Staphylococcus aureus (MIC90 values from 8.3μM to 50μM), whereas a (decyloxy)benzene substitution exhibited moderate activity against Candida albicans (MIC90 values 36μM). According to SAR evaluation, the size of the crown ether and the acyl side chain had a significant effect on the bioactivity. Aromatic moieties close to the acyl group led to improved bioactivity as exemplified by some of the tested compounds. These results provide further evidence on the potential of crown ethyl structure as a scaffold for developing new biological probes and lead candidates for drug development.