Ferulic Acid Inhibits Topoisomerase I of Mycobacterium Tuberculosis

Abstract

IntroductionVarious drugs are first line anti-TB drugs for more than thirty years. Since ferulic acid have shown promising inhibition growth of M. tuberculosis and M. smegmatis cell.ObjectiveIn this study, we have explored the inhibitory effect of ferulic acid against Mycobacterium tuberculosis topoisomerase I. We further investigated the mechanism of ferulic acid by various experiments.MethodsDNA relaxation assays was done for supercoiled pUC18 DNA, oligonucleotide cleavage assay was performed for 5ʹ-end-labeled 32-mer harboring the STS (Strong Topoisomerase Site) annealed to a complimentary sequence. Growth inhibition (MIC) values were calculated by performing resazurin reduction microplate assay (REMA).ResultsIn this study, we describe the growth inhibition of M. tuberculosis and M. smegmatis through Mycobacterium tuberculosis topoisomerase I (MttopoI) by ferulic acid. We have further investigated the mechanism of ferulic acid by analysing the two step of topoisomerase 1 (topoI) reaction cycle. Ferulic acid was able to stimulate cleavage which further leads to cleavage-relegation equilibrium. Moreover, it was shown that ferulic acid inhibited topoI overexpressing cells at low minimum inhibitory concentration (MIC). Ferulic acid affects the activity of DNA relexation in the mutations in DxDxE motif of metal binding mutants which contributes to the reaction of enzyme with the drug.ConclusionIn conclusion, our results indicate that ferulic acid leads to combat microbial infection and act as toxins to MstopoI and MttopoI. Moreover, targeting metal coordination to topoisomerases might be a general strategy to develop new lead molecules.

Effects of In Vitro Digestion of Polyphenols from Coffee on Binding Parameters to Human Topoisomerase II α

“…It is worth noting that ferulic acid bound as a competitive inhibitor ( Figure 1 D). This was observed in the present study as well as the study by Lu et al [ 27 ], who reported that ferulic acid can act as a competitive inhibitor of TOP at a concentration of 10–30 µM. The cited study showed that ferulic acid can inhibit cell proliferation in Procaryote by directly binding the DNA-gyrase complex [ 27 ].…”

“…This was observed in the present study as well as the study by Lu et al [27], who reported that ferulic acid can act as a competitive inhibitor of TOP at a concentration of 10-30 µM. The cited study showed that ferulic acid can inhibit cell proliferation in Procaryote by directly binding the DNA-gyrase complex [27]. Additionally, Bandele et al [28] reported that polyphenols are a diverse and complex group of compounds that interact with the enzyme in a noncovalent manner but can also react by covalent adduction.…”