(Hp)tlc-Bioautography-ms/nmr – A New Tool for the Search of Anti-Tuberculosis Lead Compounds

(HP)TLC-Bioautography-MS/NMR is a new method developed to respond to the quest for new anti-tuberculosis lead compounds and to overcome the limitations of the classical bioactivity-guided isolation concept. By combining modern microbiology, chromatographic, and spectrometric methods in a multidimensional setting, it is possible to obtain structural information about the compound of interest in an early purification step, and also overcome the challenges associated with (i) long isolation procedures, (ii) the frequent oversight of minor but highly-active compounds, (iii) the monitoring of anti-TB activity during fractionation, and (iv) the loss of bioactivity due to “synergistic” effects. Exemplary applications involving actinomycete and Aspergillus extracts with anti-TB activity demonstrate that the new, integrated methodology enables the identification and/or isolation of new and known anti-TB compounds. Thus, TLC-Bioautography-MS/NMR methodology is fit for the purpose of TB drug discovery from natural sources. [Funding: NIH grant 5 R21 AI093919 – 02]