Macrocyclic peptidomimetics with antimicrobial activity: synthesis,

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 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.

C1 [Ibrahim, Mohamed A.; Panda, Siva S.; Oliferenko, Alexander A.; Oliferenko, Polina V.; Elagawany, Mohamed; Kucukbay, F. Zehra; Panda, Chandramukhi S.; Pillai, Girinath G.; Hall, C. Dennis; Katritzky, Alan R.] Univ Florida, Dept Chem, Gainesville, FL 32611 USA.

[Ibrahim, Mohamed A.] Misr Univ Sci & Technol, Coll Pharm, Dept Organ Chem, Soaad Kafafi, Giza Governorat, Egypt.

[Ibrahim, Mohamed A.] Almaarefa Coll Sci & Technol, Dept Pharmaceut Chem, Riyadh 11597, Saudi Arabia.

[Panda, Siva S.] Georgia Reagents Univ, Dept Chem & Phys, Augusta, GA 30912 USA.

[Girgis, Adel S.] Natl Res Ctr, Dept Pesticide Chem, Giza 12622, Egypt.

[Elagawany, Mohamed] Damanhour Univ, Fac Pharm, Dept Pharmaceut Chem, Damanhour, Egypt.

[Kucukbay, F. Zehra] Inonu Univ, Fac Pharm, Dept Basic Pharmaceut Sci, TR-44280 Malatya, Turkey.

[Pillai, Girinath G.; Tamm, Kaido] Univ Tartu, Dept Chem, EE-50411 Tartu, Estonia.

[Samir, Ahmed] Cairo Univ, Fac Vet Med, Dept Microbiol, Cairo, Egypt.