4404-45-9Relevant articles and documents
Synthesis and structure-activity relationships of aliphatic isothiocyanate analogs as antibiotic agents
Li, Deguang,Shu, Yanan,Li, Pingliang,Zhang, Wenbing,Ni, Hanwen,Cao, Yongsong
, p. 3119 - 3125 (2013)
Isothiocyanates (ITCs) are one of the many classes of breakdown products of glucosinolates found in plants and exhibit biologic activity against various pathogens. In this work, aliphatic isothiocyanates were prepared and the antimicrobial activities against plant pathogenic fungi and bacteria were tested to understand the structure-activity relationships. The results indicated that longer-chain derivatives exert a steric inhibition on toxicity of ITCs against Rhizoctonia solani because of steric hindrance and the order of the eight aliphatic ITCs was ethyl > n-propyl > methyl > n-hexyl > n-octyl > n-butyl > n-heptyl > n-pentyl. Because the hydrophobicity of ITCs was enhanced by increasing alkyl chain length, the antibacterial activity of ITCs against Erwinia carotovora was moderately intense with an increase in hydrophobicity and the order was n-octyl > n-pentyl > n-heptyl > n-hexyl > n-propyl > n-butyl > methyl > ethyl. The present study revealed that some of the compounds exhibited promising antimicrobial activity and could be used as an acceptable alternative to the traditional synthetic fungicides for controlling R. solani and E. carotovora.
4-Alkyl-1,2,4-triazole-3-thione analogues as metallo-β-lactamase inhibitors
Gavara, Laurent,Legru, Alice,Verdirosa, Federica,Sevaille, Laurent,Nauton, Lionel,Corsica, Giuseppina,Mercuri, Paola Sandra,Sannio, Filomena,Feller, Georges,Coulon, Rémi,De Luca, Filomena,Cerboni, Giulia,Tanfoni, Silvia,Chelini, Giulia,Galleni, Moreno,Docquier, Jean-Denis,Hernandez, Jean-Fran?ois
, (2021/06/15)
In Gram-negative bacteria, the major mechanism of resistance to β-lactam antibiotics is the production of one or several β-lactamases (BLs), including the highly worrying carbapenemases. Whereas inhibitors of these enzymes were recently marketed, they only target serine-carbapenemases (e.g. KPC-type), and no clinically useful inhibitor is available yet to neutralize the class of metallo-β-lactamases (MBLs). We are developing compounds based on the 1,2,4-triazole-3-thione scaffold, which binds to the di-zinc catalytic site of MBLs in an original fashion, and we previously reported its promising potential to yield broad-spectrum inhibitors. However, up to now only moderate antibiotic potentiation could be observed in microbiological assays and further exploration was needed to improve outer membrane penetration. Here, we synthesized and characterized a series of compounds possessing a diversely functionalized alkyl chain at the 4-position of the heterocycle. We found that the presence of a carboxylic group at the extremity of an alkyl chain yielded potent inhibitors of VIM-type enzymes with Ki values in the μM to sub-μM range, and that this alkyl chain had to be longer or equal to a propyl chain. This result confirmed the importance of a carboxylic function on the 4-substituent of 1,2,4-triazole-3-thione heterocycle. As observed in previous series, active compounds also preferentially contained phenyl, 2-hydroxy-5-methoxyphenyl, naphth-2-yl or m-biphenyl at position 5. However, none efficiently inhibited NDM-1 or IMP-1. Microbiological study on VIM-2-producing E. coli strains and on VIM-1/VIM-4-producing multidrug-resistant K. pneumoniae clinical isolates gave promising results, suggesting that the 1,2,4-triazole-3-thione scaffold worth continuing exploration to further improve penetration. Finally, docking experiments were performed to study the binding mode of alkanoic analogues in the active site of VIM-2.
Organophosphine-free copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur
Feng, Wei,Zhang, Xing-Guo
supporting information, p. 1144 - 1147 (2019/01/28)
A copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur in the absence of organophosphine has been established. This approach represents a simple and efficient one-pot synthesis of isothiocyanates, and features excellent functional group tolerance and the use of a cheap, safe and odorless sulfur source. Moreover, this process could directly provide isothiocyanate analogous bioactive molecules, thiocarbonyl-containing pesticides and facile construction of benzoxazole and benzimidazole frames.
