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


IBRAHIM M. A. , PANDA S. S. , OLIFERENKO A. A. , OLIFERENKO P. V. , GIRGIS A. S. , ELAGAWANY M., ...Daha Fazla

ORGANIC & BIOMOLECULAR CHEMISTRY, cilt.13, ss.9492-9503, 2015 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 13 Konu: 36
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1039/c5ob01400j
  • Dergi Adı: ORGANIC & BIOMOLECULAR CHEMISTRY
  • Sayfa Sayıları: ss.9492-9503

Özet

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 poly-pharmacological 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.