Macrocyclic peptidomimetics with antimicrobial activity: synthesis, bioassay, and molecular modeling studies

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry. Microbiological testing of the synthesized compounds revealed an exceptionally high activity against Candida albicans with a minimum inhibitory concentration (MIC) two orders of magnitude lower than the MIC of the antifungal reference drug amphotericin B. A strikingly high activity was also observed against three Gram-negative bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris), two of which are known human pathogens. Thus the discovered chemotype is a potential polypharmacological agent. The toxicity against mammalian tumor cells was found to be low, as demonstrated in five different human cell lines (HeLa, cervical; PC-3, prostate; MCF-7, breast; HepG2, liver; and HCT-116, colon). The internal consistency of the experimental data was studied using 3D-pharmacophore and 2D-QSAR.

Original languageEnglish (US)
Pages (from-to)9492-503
Number of pages12
JournalOrganic and Biomolecular Chemistry
Issue number36
StatePublished - Sep 28 2015


  • Anti-Bacterial Agents
  • Antifungal Agents
  • Candida albicans
  • Cell Line, Tumor
  • Cell Proliferation
  • Dose-Response Relationship, Drug
  • Gram-Negative Bacteria
  • Humans
  • Macrocyclic Compounds
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Peptidomimetics
  • Quantitative Structure-Activity Relationship
  • Journal Article
  • Research Support, Non-U.S. Gov't


Dive into the research topics of 'Macrocyclic peptidomimetics with antimicrobial activity: synthesis, bioassay, and molecular modeling studies'. Together they form a unique fingerprint.

Cite this