1-(2-Hydroxybenzoyl)-thiosemicarbazides are promising antimicrobial agents targeting
A series of 1-(2-hydroxybenzoyl)thiosemicarbazides I [R1 = H, 2-OH, 4-F, etc.; R2 = Ph, 1-naphthyl, 3-pyridinyl, etc.] inhibitors of D-Ala-D-Ala ligase (Ddl) were designed and synthesized in order to target resistant strains of bacteria. Among these, compound I [R1 = 2-OH, R2 = 3,4-di-ClC6H3] was identified as a potent Ddl inhibitor with activity in the micromolar range. This compound, possessing strong antimicrobial activity including against multidrug resistant strains, was proven to act through a bactericidal mechanism and demonstrated very low cytotoxicity on THP-1 human monocytic cell line. Inhibition of Ddl activity by compound I compound I [R1 = 2-OH, R2 = 3,4-di-ClC6H3] was confirmed in-bacterio using UPLC-MS/MS by demonstrating an increase in D-Ala intracellular pools accompanied by a commensurate decrease in D-Ala-D-Ala. Further structure-activity relationships (SARs) studies provided evidence that the hydroxyl substituent in the 2-position (R1) of the benzoylthiosemicarbazide scaffold was essential for the enzymic inhibition. This work thus highlightened the 1-(2-hydroxybenzoyl)-thiosemicarbazide motif as a very promising tool for the development of novel antibacterial compounds acting through an interesting mechanism of action and low cytotoxicity. In the experiment, the researchers used many compounds, for example, 2,4-Dichlorophenylisothiocyanate (cas: 6590-96-1Application of 6590-96-1).
2,4-Dichlorophenylisothiocyanate (cas: 6590-96-1) belongs to organic chlorides. Chlorination modifies the physical properties of hydrocarbons in several ways. These compounds are typically denser than water due to the higher atomic weight of chlorine versus hydrogen. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Application of 6590-96-1
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics