Semisynthesis of Platensimycin Derivatives with Antibiotic Activities in Mice via Suzuki–Miyaura Cross-Coupling Reactions

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Platensimycin (PTM), originally isolated from soil bacteria Streptomyces platensis , is a potent FabF inhibitor against many gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. However, the further clinical development of PTM is hampered by its poor bioavailability. In this study, twenty PTM derivatives were prepared by Suzuki-Miyaura cross-coupling reactions catalyzed by Pd (0)/C. Compared to PTM, 6-pyrenyl PTM ( 6t ) showed improved antibacterial activity against MRSA in a mouse peritonitis model. Our results support the strategy to target the essential fatty acid synthases in major pathogens, in order to discover and develop new generations of antibiotics.

Related collections

Author and article information

Journal

Title: Journal of Medicinal Chemistry

Abbreviated Title: J. Med. Chem.

Publisher: American Chemical Society (ACS)

ISSN (Print): 0022-2623

ISSN (Electronic): 1520-4804

Publication date Created: December 05 2018

Publication date (Electronic): December 05 2018

Affiliations

[1 ]Xiangya International Academy of Translational Medicine at Central South University, Changsha, Hunan 410013, China

[2 ]Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discovery, Changsha, Hunan 410011, China

[3 ]National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery, Changsha, Hunan 410011, China

Article

DOI: 10.1021/acs.jmedchem.8b01580

PMC ID: 7110910

PubMed ID: 30461269

SO-VID: 97eaf635-32c8-4c9a-980b-6a89e38dba4e

History

Data availability:

Comments

Comment on this article

scite_

Cited by 2

See all cited by

- Version 1
- Version 1