Design, synthesis, and evaluation of curcumin analogues as potential inhibitors of bacterial sialidase. (1st January 2018)

• Record Type: Journal Article
• Authors: Kim, Bo Ram; Park, Ji-Young; Jeong, Hyung Jae; Kwon, Hyung-Jun; Park, Su-Jin; Lee, In-Chul; Ryu, Young Bae; Lee, Woo Song
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 33:Number 1(2018)
• Page Start: 1256
• Page End: 1265
• Publication Date: 2018-01-01
• Subjects: Curcumin -- sepsis -- sialidase -- Nan A; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2018.1488695
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Sialidases are key virulence factors that remove sialic acid from the host cell surface glycan, unmasking receptors that facilitate bacterial adherence and colonisation. In this study, we developed potential agents for treating bacterial infections caused by Streptococcus pneumoniae Nan A that inhibit bacterial sialidase using Turmeric and curcumin analogues. Design, synthesis, and structure analysis relationship (SAR) studies have been also described. Evaluation of the synthesised derivatives demonstrated that compound5e was the most potent inhibitor of S. pneumoniae sialidase (IC50 = 0.2 ± 0.1 µM). This compound exhibited a 3.0-fold improvement in inhibitory activity over that of curcumin and displayed competitive inhibition. These results warrant further studies confirming the antipneumococcal activity5e and indicated that curcumin derivatives could be potentially used to treat sepsis by bacterial infections.