Fig. 4: Chemical competition assay reveals that BZT’s activity is mediated through blocking HRH1.

In Mtb-infected THP-1 macrophages; a addition of histamine (HIS, 10 µM), the natural ligand of the H1 receptor, blocked BZT (30 µM)-mediated inhibition of intracellular Mtb growth and b pyrilamine (PYR, 50 µM), an HRH1 antagonist, exhibited intracellular activity against Mtb. Graphs showing % intracellular Mtb growth inhibition of; c eight FDA-approved H1 antagonists (50 µM each) and; d BZT (25 µM) and seventeen other structural analogues of BZT (25 µM each) in Mtb infected THP-1 macrophages all the tested compounds were added to the media 3 h post infection and Mtb growth inhibition was determined 72 h post infection. e Chemical structure of two of the BZT analogues with higher anti-Mtb potency than BZT. NT non-treated control. Data represent the mean ± SEM of at least two independent experiments. Statistical significance was determined using an unpaired T-test; ***p < 0.001, **p < 0.005, *p < 0.05; ns non-significant.