Design, synthesis, and evaluation of curcumin analogues as potential inhibitors of bacterial sialidase

<p>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 <i>Streptococcus pneumoniae</i> Nan A that inhibit bacterial sialidase using <i>Turmeric</i> and curcumin analogues. Design, synthesis, and structure analysis relationship (SAR) studies have been also described. Evaluation of the synthesised derivatives demonstrated that compound <b>5e</b> was the most potent inhibitor of <i>S. pneumoniae</i> sialidase (IC<sub>50</sub> = 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 activity <b>5e</b> and indicated that curcumin derivatives could be potentially used to treat sepsis by bacterial infections.</p>