Macrocyclic peptidomimetics with antimicrobial activity: synthesis, bioassay, and molecular modeling studiesElectronic supplementary information (ESI) available: Including 1H NMR, 13C NMR, CHN/HRMS, Tables of descriptor models, 3D-pharmacophore mapped models and Dose-response curves of all the compounds. See DOI: 10.1039/c5ob01400j

• Main Authors: Ibrahim, Mohamed A, Panda, Siva S, Oliferenko, Alexander A, Oliferenko, Polina V, Girgis, Adel S, Elagawany, Mohamed, Küçükbay, F. Zehra, Panda, Chandramukhi S, Pillai, Girinath G, Samir, Ahmed, Tämm, Kaido, Hall, C. Dennis, Katritzky, Alan R
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c5ob01400j

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. Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry.