title: Macrocyclic peptidomimetics with antimicrobial activity: synthesis, bioassay, and molecular modeling studies.
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.
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA. drmmonem@yahoo.com sspanda12@gmail.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ibrahim
authors.forename: Siva S
authors.initials: SS
authors.lastname: Panda
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Oliferenko
authors.forename: Polina V
authors.initials: PV
authors.lastname: Oliferenko
authors.forename: Adel S
authors.initials: AS
authors.lastname: Girgis
authors.forename: Mohamed
authors.initials: M
authors.lastname: Elagawany
authors.forename: F Zehra
authors.initials: FZ
authors.lastname: Küçükbay
authors.forename: Chandramukhi S
authors.initials: CS
authors.lastname: Panda
authors.forename: Girinath G
authors.initials: GG
authors.lastname: Pillai
authors.forename: Ahmed
authors.initials: A
authors.lastname: Samir
authors.forename: Kaido
authors.initials: K
authors.lastname: Tämm
authors.forename: C Dennis
authors.initials: CD
authors.lastname: Hall
authors.forename: Alan R
authors.initials: AR
authors.lastname: Katritzky
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D047028:Macrocyclic Compounds; D057786:Peptidomimetics