Putative histidine kinase inhibitors with antibacterial effect against multi-drug resistant clinical isolates identified by in vitro and in silico screens was written by Velikova, Nadya;Fulle, Simone;Manso, Ana Sousa;Mechkarska, Milena;Finn, Paul;Conlon, J. Michael;Oggioni, Marco Rinaldo;Wells, Jerry M.;Marina, Alberto. And the article was included in Scientific Reports in 2016.Formula: C9H7ClN2S This article mentions the following:
Novel antibacterials are urgently needed to address the growing problem of bacterial resistance to conventional antibiotics. Two-component systems (TCS) are widely used by bacteria to regulate gene expression in response to various environmental stimuli and physiol. stress and have been previously proposed as promising antibacterial targets. TCS consist of a sensor histidine kinase (HK) and an effector response regulator. The HK component contains a highly conserved ATP-binding site that is considered to be a promising target for broad-spectrum antibacterial drugs. Here, we describe the identification of putative HK autophosphorylation inhibitors following two independent exptl. approaches: in vitro fragment-based screen via differential scanning fluorometry and in silico structure-based screening, each followed up by the exploration of analog compounds as identified by ligand-based similarity searches. Nine of the tested compounds showed antibacterial effect against multi-drug resistant clin. isolates of bacterial pathogens and include three novel scaffolds, which have not been explored so far in other antibacterial compounds Overall, putative HK autophosphorylation inhibitors were found that together provide a promising starting point for further optimization as antibacterials. In the experiment, the researchers used many compounds, for example, 4-(2-Chlorophenyl)thiazol-2-amine (cas: 21344-90-1Formula: C9H7ClN2S).
4-(2-Chlorophenyl)thiazol-2-amine (cas: 21344-90-1) belongs to thiazole derivatives. Thiazoles frequently appear in peptide studies. Thiazoles can also be used as protected formyl groups, which can be released in later stages of complex natural product synthesis. Various laboratory methods exist for the organic synthesis of thiazoles. Prominent is the Hantzsch thiazole synthesis is a reaction between haloketones and thioamides.Formula: C9H7ClN2S
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica