Table 1.

Biochemical and cellular activity of InhA inhibitors described in the literature (Fig. 1) that show cellular activity in Mycobacterium tuberculosis

CompoundReported affinity, nMCellular activity: MIC50, µM (H37Rv)cLogPLLEPredominant InhA binding
10.79*0.158−0.79.8Apo
20.0210.0007.03.7NAD+
36309.57§0.3983.12.1Apo
43.16§0.1992.36.2NADH
53.980.501#1.47.0ND
6630.960.0795.30.9NADH
  • cLogP, the calculated logarithms of water-octanol partition coefficients; LLE, log10 of reported affinity − cLogP; ND, not determined.

  • * Ki measurement.

  • cLogP calculated for prodrug isoniazid rather than active drug INH-NAD adduct.

  • K1 measurement.

  • § Kd measurement.

  • IC50.

  • # MIC90.

  • A close analog, NITD-529, showed binding only to NADH form of InhA.