2. Academic Validation
  3. Synthesis and biological evaluation of crown ether acyl derivatives

Synthesis and biological evaluation of crown ether acyl derivatives

  • Bioorg Med Chem Lett. 2016 Nov 15;26(22):5591-5593. doi: 10.1016/j.bmcl.2016.09.066.
Martín Febles 1,  Sofía Montalvão 2,  Guillermo Díaz Crespín 1,  Manuel Norte 1,  José M Padrón 1,  Päivi Tammela 3,  José J Fernández 4,  Antonio Hernández Daranas 5
Affiliations

Affiliations

  • 1 Instituto Universitario de Bio-Organica Antonio Gonzalez (IUBO AG), Universidad de La Laguna, Avenida Francisco Sánchez 2, 38205 La Laguna, Spain.
  • 2 Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, PO Box 56, FI-00014 University of Helsinki, Finland.
  • 3 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.
  • 4 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.
  • 5 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.
PMID: 27765506 DOI: 10.1016/j.bmcl.2016.09.066
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 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.

Keywords

18-Crown-6; Antimicrobial; Antiproliferative; Crown ether; Structure–activity.

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