Abstract
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 language | English (US) |
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Pages (from-to) | 9492-503 |
Number of pages | 12 |
Journal | Organic and Biomolecular Chemistry |
Volume | 13 |
Issue number | 36 |
DOIs | |
State | Published - Sep 28 2015 |
Keywords
- 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