Mycobacterium tuberculosis thymidylate synthase (ThyX) is a target for plumbagin, a natural product with antimycobacterial activity

摘要: Plumbagin derived from the plant Plumbago indica, known as Chitrak in India, is an example of a medicinal compound used traditionally to cure variety ailments. Previous reports have indicated that it can inhibit growth Mycobacterium tuberculosis (Mtb), causative agent deadly disease TB. In this investigation, we provide insight into its mode action. We show here significant mycobacterial target inhibited by plumbagin enzyme ThyX, form thymidylate synthase, responsible for synthesis dTMP dUMP various bacterial pathogens, including Mtb. Using purified preparation recombinant version Mtb demonstrate plumbagin, 2,4 napthoquinone, but not lawsone, structurally related compound, inhibits activity vitro. also intracellular [dTTP]/[dATP] ratio smegmatis (Msm) cells decrease upon treatment with and this, turn, leads cell death. Such conclusion supported observation over-expression thyx treated Msm restoration viability. The results our investigation indicate kills primarily targeting vital required their survival.