| Literature DB >> 29363971 |
Anish Parmar, Rajamani Lakshminarayanan1, Abhishek Iyer2, Venkatesh Mayandi1, Eunice Tze Leng Goh1, Daniel G Lloyd, Madhavi Latha S Chalasani3, Navin K Verma1,3, Stephen H Prior, Roger W Beuerman1, Annemieke Madder2, Edward J Taylor, Ishwar Singh.
Abstract
The cyclic depsipeptide, teixobactin, kills a number of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium tuberculosis without detectable resistance. To date, teixobactin is the only molecule in its class that has shown in vivo antibacterial efficacy. In this work, we designed and synthesized 10 new in vivo ready teixobactin analogues. These analogues showed highly potent antibacterial activities against Staphylococcus aureus, MRSA, and vancomycin-resistant enterococci (VRE) in vitro. One analogue, d-Arg4-Leu10-teixobactin, 2, was found to be noncytotoxic in vitro and in vivo. Moreover, topical instillation of peptide 2 in a mouse model of S. aureus keratitis decreased the bacterial bioburden (>99.0% reduction) and corneal edema significantly as compared to untreated mouse corneas. Collectively, our results have established the high therapeutic potential of a teixobactin analogue in attenuating bacterial infections and associated severities in vivo.Entities:
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Year: 2018 PMID： 29363971 DOI： 10.1021/acs.jmedchem.7b01634
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446