The situation with drug resistant forms of tuberculosis (TB), aka MDR and XDR forms, remains increasingly troubling. XDR form was originally identified in 2006 and by now comprising up to 30-50% cases in some regions of South Africa and India. 30% HIV-positive patients with XDR TB are dead within a few months. The world’s R&D spendings against TB are around $150M/year. With new drugs costs approaching $1B, the current budget hardly allows for getting a single new drug in 5-10years. This is in spite of the fact that XDR TB treatment would require a cocktail of a few novel and highly efficient drugs.
QUANTUM drug discovery platform is developed with the idea of bringing down the drug discovery costs and may well be the lacking tool to bring up the long awaited, cheap and effective medications against TB. We designed a series of highly potent compounds targeting vital proteins within a TB organism “chain of command”. The lead candidates were subsequently tested and optimized in vitro. The lead compound so far, QP-42, is able to kill TB bacteria at concentrations as low as 3-11mug/ml (see the graph below).
The anti-tuberculosis action of QP-42 was studied by observing M.tuberculosis H37Rv bacteria growth with/without the active compound at various concentrations (we show the results for 3,70 mkg/ml, 11,11 mkg/ml. The bacteria count growth was studied using the automated system Bactec MGIT 960 (Becton Dickenson, USA). The setup is designed such that the samples fluorescence is directly proportional to the oxygen consumptions by micobacteria. Therefore, the more bacteria are present in a sample, the more fluorescence signal is collected and plotted on the Figure above. The bacteria population growth detection was performed every hour and processed with Epicenter software(Becton Dickenson, USA) and plotted in relative units of fluorescence (see the blue and the green lines corresponding to 3,70 mkg/ml, 11,11 mkg/ml). The horizontal axis shows the number of days passed since the beginning of the experiment.
The inhibiting activity determination research of QP-1942 with the help of Bactec MGIT960 system showed complete suppression of growth of M.tuberculosis H37Rv at concentrations of 11.11 micrograms. The cultivation of M.tuberculosis H37Rv with the drug at a concentration of 3.70 mg / ml resulted in a significant delay in growth of the culture (14 days). The concentration of the drug 1,23 mg / ml resulted in significantly delay the growth of the culture at 1 day compared with the control.
Thus, the drug QP-42 had a bacteriostatic activity against laboratory sensitive strain M.tuberculosis H37Rv, inhibitory concentration value was equal to 11.11 mg / ml.
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