Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10591801 | Bioorganic & Medicinal Chemistry Letters | 2014 | 7 Pages |
Abstract
We describe the synthesis and antimicrobial evaluation of structurally new peptidomimetics, rich in synthetically modified l-histidine. Two series of tripeptidomimetics were synthesized by varying lipophilicity at the C-2 position of l-histidine and at the N- and C-terminus. The data indicates that peptides (5f, 6f, 9f and 10f) possessing highly lipophilic adamantan-1-yl group displayed strong inhibition of Cryptococcus neoformans. Peptide 6f is the most potent of all with IC50 and MFC values of 0.60 and 0.63 μg/mL, respectively, compared to the commercial drug amphotericin B (IC50 = 0.69 and MFC = 1.25 μg/mL). The selectivity of these peptides to microbial pathogen was examined by a tryptophan fluorescence quenching study and transmission electron microscopy. These studies indicate that the peptides plausibly interact with the mimic membrane of pathogen by direct insertion, and results in disruption of membrane of pathogen.
Keywords
DMFEYPGO-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborateC. neoformanstert-butoxycarbonylEYPCDIEATBTUBOCHOBtMICIC50DICTrp1-hydroxybenzotriazole1,3-diisopropylcarbodiimideN,N-dimethylformamideN,N-diisopropylethylamineAlkylationamino acidTemTryptophanMinimum inhibitory concentrationmicrowaveMethanolMeOHTransmission electron microscopyAntifungal peptides
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Amit Mahindra, Nitin Bagra, Nishima Wangoo, Rohan Jain, Shabana I. Khan, Melissa R. Jacob, Rahul Jain,