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. 2021 Aug 4;14(8):768. doi: 10.3390/ph14080768

Table 1.

Prepared compounds ordered by increasing calculated lipophilicity (log P) with their antimycobacterial activity expressed as minimum inhibitory concentration (MIC) and HepG2 cytotoxicity.

graphic file with name pharmaceuticals-14-00768-i001.jpg
Cmpd R LogP MIC µg/mL (µM) HepG2 SI ††
Mtb H37Ra M. smeg M. aurum IC50 (µM)
1 H 2.43 ≥500 ≥250 ≥250 >50 †
2 3-OH 2.04 15.625 (58.9) ≥125 ≥125 >250 † >4.20
3 4-OH 2.04 62.5 (235.6) ≥500 ≥500 >250 † >1.01
4 3,5-diOCH3 2.18 62.5 (202) ≥125 ≥125 >25 † >0.12
5 4-OCH3 2.31 ≥125 ≥125 ≥125 >50 †
6 Cyclohexyl * 2.32 31.25 (122.4) 31.25 ≥500 >1000 >8.17
7 2-F 2.59 ≥500 62.5 ≥500 >100 †
8 3-F 2.59 250 ≥500 ≥500 >100 †
9 4-F 2.59 15.625 (58.5) ≥500 ≥500 >100 † >1.71
10 4-N(CH3)2 2.72 ≥500 ≥500 ≥500 >250 †
11 2,4-diF 2.75 ≥500 ≥500 ≥500 >250 †
12 2-Cl 2.99 ≥125 ≥125 ≥125 >50 †
13 3-Cl 2.99 ≥500 ≥500 ≥500 >25 †
14 3-CF3 3.35 ≥500 ≥125 ≥125 >25 †
graphic file with name pharmaceuticals-14-00768-i002.jpg
Cmpd R LogP MIC µg/mL (µM) HepG2 SI ††
Mtb H37Ra M. smeg M. aurum IC50 (µM)
15 H 2.50 15.625 (59.3) ≥125 ≥125 >1000 >17
16 3-OH 2.11 31.25 (111.9) 62.5 ≥ 500 600.7 5.40
17 4-OH 2.11 62.5 (223.8) ≥500 500 >250 † >1.1
18 2,5-diOCH3 2.25 3.91 (12.1) ≥500 ≥500 >1000 82.60
19 3-OCH3 2.38 15.625 (47) ≥500 ≥500 >1000 >21.3
20 4-OCH3 2.38 3.91 (11.8) ≥250 125 209.4 16.1
21 3-F 2.66 7.81 (27.8) ≥500 ≥500 248.0 8.92
22 2,4-diF 2.75 ≥500 ≥500 ≥500 >25 †
23 2-CH3 2.99 7.81 (28.2) ≥125 ≥125 156.7 5.60
24 4-CH3 2.99 7.81 (28.2) ≥250 ≥250 87.7 3.11
25 2-Cl 3.06 15.625 (52.5) ≥500 ≥500 527.5 22.45
26 3-Cl 3.06 7.81 (26.2) 31.25 31.25 140.1 5.34
27 4-Br 3.33 7.81 (22.8) ≥500 ≥500 >100 † >4.4
28 3-CF3 3.42 3.91 (11.8) 250 ≥500 48.6 4.12
29 Naphthyl ** 3.50 ≥250 ≥125 ≥125 37.3
30 2,4-diCl 3.62 ≥500 ≥125 ≥125 >100 †
31 3,4-diCl 3.62 7.81 (23.5) ≥500 ≥500 66.9 2.80
graphic file with name pharmaceuticals-14-00768-i003.jpg
Cmpd R LogP MIC µg/mL (µM) HepG2 SI ††
Mtb H37Ra M. smeg M. aurum IC50 (µM)
32 H 2.78 ≥500 ≥500 ≥500 >1000
graphic file with name pharmaceuticals-14-00768-i004.jpg
Cmpd R LogP MIC µg/mL (µM) HepG2 SI ††
Mtb H37Ra M. smeg M. aurum IC50 (µM)
33 H 3.20 15.625 (53.6) ≥500 ≥500 145.9 2.7
Standards LogP MIC µg/mL (µM) HepG2 SI ††
Mtb H37Ra M. smeg M. aurum IC50 (µM)
PZA −1.31 ≥500 (≥4061) ††† ≥500 ≥500 >1000
INH −0.64 0.25 (1.82) 15.625 3.91 >1000 >459.5
CPX 1.32 0.25 (0.75) 0.125 0.0156 >500 † >666.7
RIF 4.24 0.003125 (0.0038) 12.5 0.39 >500 † >131.579
Tamoxifen 6.07 na na na 19.56 na
* Inline graphic ** Inline graphic

† Measurements at higher concentrations were not feasible due to precipitation in the testing medium. †† Selectivity index (SI) = IC50 (µM)/MIC Mtb H37Ra (µM). ††† PZA is inactive at pH 6.6 (pH of testing medium), activity is observed in acidic medium (MIC at pH of 6 is <3.91 µg/mL) [16]. * Structure of compound 6. ** Structure of compound 29.