title: Synthesis and biological evaluation of crown ether acyl derivatives.
abstract: 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 GI50values in the range of 3.7-5.6μM. Antimicrobial evaluation showed that three polyaromatic compounds were active against Staphylococcus aureus (MIC90values from 8.3μM to 50μM), whereas a (decyloxy)benzene substitution exhibited moderate activity against Candida albicans (MIC90values 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.
authors.affiliation: Instituto Universitario de Bio-Organica Antonio Gonzalez (IUBO AG), Universidad de La Laguna, Avenida Francisco Sánchez 2, 38205 La Laguna, Spain.
authors.forename: Martín
authors.initials: M
authors.lastname: Febles
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, PO Box 56, FI-00014 University of Helsinki, Finland.
authors.forename: Sofía
authors.initials: S
authors.lastname: Montalvão
authors.affiliation: Instituto Universitario de Bio-Organica Antonio Gonzalez (IUBO AG), Universidad de La Laguna, Avenida Francisco Sánchez 2, 38205 La Laguna, Spain.
authors.forename: Guillermo Díaz
authors.initials: GD
authors.lastname: Crespín
authors.affiliation: Instituto Universitario de Bio-Organica Antonio Gonzalez (IUBO AG), Universidad de La Laguna, Avenida Francisco Sánchez 2, 38205 La Laguna, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Norte
authors.affiliation: Instituto Universitario de Bio-Organica Antonio Gonzalez (IUBO AG), Universidad de La Laguna, Avenida Francisco Sánchez 2, 38205 La Laguna, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Padrón
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, PO Box 56, FI-00014 University of Helsinki, Finland. Electronic address: paivi.tammela@helsinki.fi.
authors.forename: Päivi
authors.initials: P
authors.lastname: Tammela
authors.affiliation: Instituto Universitario de Bio-Organica Antonio Gonzalez (IUBO AG), Universidad de La Laguna, Avenida Francisco Sánchez 2, 38205 La Laguna, Spain. Electronic address: jjfercas@ull.es.
authors.forename: José J
authors.initials: JJ
authors.lastname: Fernández
authors.affiliation: Instituto Universitario de Bio-Organica Antonio Gonzalez (IUBO AG), Universidad de La Laguna, Avenida Francisco Sánchez 2, 38205 La Laguna, Spain. Electronic address: adaranas@ull.es.
authors.forename: Antonio Hernández
authors.initials: AH
authors.lastname: Daranas
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D043844:Crown Ethers / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D043844:Crown Ethers; C015762:18-crown-6
keywords: 18-Crown-6; Antimicrobial; Antiproliferative; Crown ether; Structure–activity