Dataset Information


Late-Stage Functionalization of Platensimycin Leading to Multiple Analogues with Improved Antibacterial Activity in Vitro and in Vivo.

ABSTRACT: Bacterial fatty acid synthases are promising antibacterial targets against multidrug-resistant pathogens. Platensimycin (PTM) is a potent FabB/FabF inhibitor, while its poor pharmacokinetics hampers the clinical development. In this study, a focused library of PTM derivatives was prepared through thiolysis of PTM oxirane (1), followed by various C-C cross-coupling reactions in high yields. Antibacterial screening of these compounds in vitro yielded multiple hits with improved anti-Staphylococcus activities over PTM. Among them, compounds A1, A3, A17, and A28 exhibited improved antibacterial activities over PTM against methicillin-resistant Staphylococcus aureus (MRSA) in a mouse peritonitis model. Compound A28 was further shown to be effective against MRSA infection in a mouse wound model, in comparison to mupirocin. Therefore, the facile preparation and screening of these PTM derivatives, together with their potent antibacterial activities in vivo, suggest a promising strategy to improve the antibacterial activity and pharmacokinetic properties of PTM.


PROVIDER: S-EPMC6755679 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC7110910 | BioStudies
2018-01-01 | S-EPMC6072473 | BioStudies
2014-01-01 | S-EPMC3966621 | BioStudies
2016-01-01 | S-EPMC5466352 | BioStudies
2018-01-01 | S-EPMC7105086 | BioStudies
1000-01-01 | S-EPMC3069196 | BioStudies
2017-01-01 | S-EPMC5421316 | BioStudies
2018-01-01 | S-EPMC6006322 | BioStudies
2016-01-01 | S-EPMC5063666 | BioStudies
2017-01-01 | S-EPMC5471356 | BioStudies