My Antitubercular Research: Pitfalls and Recent Discoveries

30 Mar
Published by Miguel Mitchell

I am happy to report that my group in collaboration with Scott Franzblau from the Institute for Tuberculosis Research at U. Illinois-Chicago has published our anti-TB work (see attachment). We explored the quaternized promazine derivatives as antitubercular agents, and found that the most potent thus far are 4- and 3-chlorophenyl derivatives of triflupromazine, both nontoxic in vitro against Vero cells. In our unpublished studies, we have also discovered that both of these actives are bacteriocidal against M. tuberculosis and that the 4-chlorobenzyl derivative is as bacteriocidal as rifampin, the most potent clinically prescribed antitubercular drug. So we're quite happy!

On a more sobering topic, I want to tell everyone interested in embarking upon antitubercular drug synthesis, in my opinion, you SHOULD NOT use the free MIC testing by the NIAID Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF). Before I sent my compounds to Scott for testing, TAACF obtained MIC data for me. Although I was unhappy with the time it took to receive data (> 6 months), I never doubted its veracity before. However, I soon discovered from the program director that there is no replication of any MIC measurements, not even duplicates. I may be old school, but I believe that data reproducibility and precision determination are hallmarks of good science. If you read my first blog entry, the MIC and IC50 data there came from TAACF. Please disregard it. As you can read in my attached paper, which has SD values on each MIC (almost all IC50 values were > 128 ug/mL), there is no significant overlap between the new replicate data and TAACF's single value data, even the IC50 data.

On the TAACF site, there is a public data base of MIC measurements of hundreds of compounds.
How can we trust this data if it came from single measurements? And how can referees accept TAACF data presented for publication?

I have thought a long time about whether I should broach this topic, but in the end I decided I had to because I am a US taxpayer, and I want the dollars spent on science to be spent on good science.
When TAACF changes its way of doing its MIC determinations, I will gladly support their efforts to give free access to antitubercular agent testing.