Journal
MEDICINAL RESEARCH REVIEWS
Volume 40, Issue 4, Pages 1440-1495Publisher
WILEY
DOI: 10.1002/med.21651
Keywords
antibacterial agents; histidine kinase; histidine kinase inhibitors; two-component signal transduction systems
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Funding
- French ministere de l'education nationale, de l'enseignement superieur et de la recherche
- University of Nimes
- US National Institute of General Medical Sciences, National Institutes of Health [GM106085]
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Infections caused by multidrug-resistant bacteria represent a significant and ever-increasing cause of morbidity and mortality. There is thus an urgent need to develop efficient and well-tolerated antibacterials targeting unique cellular processes. Numerous studies have led to the identification of new biological targets to fight bacterial resistance. Two-component signal transduction systems are widely employed by bacteria to translate external and cellular signals into a cellular response. They are ubiquitous in bacteria, absent in the animal kingdom and are integrated into various virulence pathways. Several chemical series, including isothiazolidones, imidazolium salts, benzoxazines, salicylanilides, thiophenes, thiazolidiones, benzimidazoles, and other derivatives deduced by different approaches have been reported in the literature to have histidine kinase (HK) inhibitory activity. In this review, we report on the design and the synthesis of these HKs inhibitors and their potential to serve as antibacterial agents.
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