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Figure 5. Graph showing the correlation between training and test set compounds.
the compounds showed rapid killing of the M. tuberculosis. The
MBC was close to the MIC confirming its bactericidal nature and
the kinetics demonstrated a potent sterilizing effect under aerobic
growth conditions. These compounds were nontoxic towards hu-
man red blood cells (hRBC) upto 500 l
g/mL concentration.32 Addi-
tionally atom-based quantitative structure–activity relationship
(QSAR) model was developed that gave a statistically satisfying re-
sult (R2) = 0.92, Q2 = 0.75, Pearson-R = 0.96 and effectively predicts
the anti-tuberculosis activity of training and test set compounds.
Acknowledgements
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36. All the synthesized compounds were evaluated for their antimycobacterial
activity against M. tuberculosis H37Rv. The minimum inhibitory concentration
(MIC) was determined for each compound using a 96-well plate format assay
in Middlebrook 7H9 medium containing 0.05% w/v Tween 80 and 10% v/v
OADC supplement (oleic acid, albumen, dextrose, catalase: Becton Dickinson).
Compounds were dissolved in DMSO and tested using a 10-point, twofold
D.S.R. thanks Council of Scientific and Industrial Research (CSIR)
[No. 02(0049)/12/EMR-II] New Delhi, India and University of Delhi,
Delhi, India for financial support. D.K. and K.K.R. are thankful to
CSIR for the award of junior and senior research fellowship and re-
search associates respectively. Authors are also thankful to CIF-
USIC, University of Delhi, Delhi for NMR spectral data and RSIC,
CDRI, Lucknow for mass data. We thank Alfredo Blakeley, Julie
Early, Stephanie Florio, and Juliane Ollinger for technical
assistance.
Supplementary data
Supplementary data associated with this article can be found, in
the
online
version,
at
serial dilution curve with the highest concentration of 20 lM and a final DMSO
concentration in the assay of 2% v/v. Growth inhibition of a recombinant strain
of M. tuberculosis was used—this strain expressed a fluorescent protein. Growth
was measured after 5 days in the presence of compound. Two readouts of
growth were used—OD590 and fluorescence. MICs were calculated after curve
fitting MICs to the Gompertz model; two points of maximum (100%) and
minimum (0%) growth were required to generate a complete curve and record
an accurate MIC. For active compounds, MICs were conducted twice using
independent cultures.
References and notes
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