Effectiveness and Properties of Hydrazide Drugs that Inhibit Growth of Mycobacterium tuberculosis

Aims: To examine the properties of hydrazide compounds shown to inhibit Mycobacterium
tuberculosis. To identify properties that affect efficiency of bacterial inhibition.
Study Design: Utilizing data from previous studies of compounds that inhibit Mycobacterium
tuberculosis, then statistical and pattern recognition methods are applied to identify interrelationships.
Place and Duration of Study: Department of Chemistry, Durham Science Center, University of
Nebraska at Omaha, from January 2016 to July 2016.
Methodology: Interrelationships of pharmacological properties were identified by use of various
pattern recognition techniques, such as hierarchical cluster analysis and path analysis. Molecular
properties and descriptors for all compounds were determined, with additional characteristics such as
structure scaffolding and functional group position was accomplished. Statistical analysis, including
Pearson r correlation, Mann-Whitney test, one-way ANOVA, Kruskal-Wallis, and descriptive statistics
were determined. Multiple regression analysis of molecular property values allows prediction of similar
compounds. Determination of any numerical outliers was accomplished by applying Grubb’s test.
Results: Compounds inhibiting the growth of Mycobacterium tuberculosis contained an aromatic ring
or were non-aromatic structures (no ring). There was weak negative correlation of MIC to formula
weight. The average formula weight, polar surface area, and Log P, is 183.55 grams/mole, 63.70 A2,
and 0.768, respectively. Values of MIC ranged from 14.7 μg/mL to 100 μg/mL. Extent of bacterial
inhibition was similar between aromatics to non-aromatics. No outliers were identified by Grubb’s test
for all values of MIC taken together. Path analysis showed polar surface area to have most effect on
MIC.
Conclusion: The measured level of growth inhibition MIC, showed strong positive relationship to
polar surface area, number of hydroxyl and amine groups, oxygen and nitrogen atoms. Two aromatic
compounds having a pyridine ring were found to be most similar to isoniazid. Aromatic and nonaromatic
compounds showed similar levels of bacterial inhibition overall.