Table 1 ADME properties of A10, A39 and A52.

From: Discovery of potent antimycobacterial agents targeting lumazine synthase (RibH) of Mycobacterium tuberculosis

Compound Code

ILOGP

XLOGP3

WLOGP

MLOGP

SILICOS-IT

Consensus LOG PO/W

Water solubility LOG S (ESOL)

Water solubility LOG S (Ali)

Water solubility LOG S (SILICOS-IT)

GI absorption

BBB permeant

Bioavailability score

P-glycoprotein substrate

CYP inhibition

A10

1.89

2.47

2.59

1.43

1.16

1.91

−3.52 (soluble)

−4.75 (moderately soluble)

−4.43 (moderately soluble)

High

No

0.55

No

CYP1A2 (Y), CYP2C19 (Y), CYP2C9 (Y), CYP2D6 (N), CYP3A4 (N)

A39

2.16

3.10

3.24

1.95

1.80

2.45

−4.12 (moderately soluble)

−5.41 (moderately soluble)

−5.03 (moderately soluble)

High

No

0.55

No

CYP1A2 (Y), CYP2C19 (Y), CYP2C9 (Y), CYP2D6 (N), CYP3A4 (N)

A52

2.30

2.83

2.90

1.69

1.66

2.28

−3.82 (soluble)

−5.13 (moderately soluble)

−4.81 (moderately soluble)

High

No

0.55

No

CYP1A2 (Y), CYP2C19 (Y), CYP2C9 (Y), CYP2D6 (N), CYP3A4 (N)

  1. Interpretation note: as calculated by SwissADME36, all the compounds are predicted to have moderate to good solubility with high gastrointestinal (GI) absorption. The Lipophilicity is > 1 and < 5, indicating good oral absorption. Bioavailability of 0.55 indicates these drugs to be good candidates for further preclinical evaluation. None of the drug molecules are substrate for P-glycoprotein induction hence, are going to be bioavailable and have good bio distribution. As only 3 out of 5 CYP450 family of enzymes are inhibited suggesting that drugs may have high intracellular retention, but can be metabolized by the residual 2 CYP450 enzymes and can possibly be cleared by the renal system. They are anticipated to have low drug-drug interaction and low toxicity. None of the compounds are predicted to cross BBB—blood brain barrier.
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