Glucuronidation activity and main structural and electronic features of catechols used for PLS modeling
| No. | Compound Name | RLM | RLM-3MC | 2B1 | 1A6 | log RLM | log 3-MC | Log P | pKa | Vm |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 4-Nitrocatechol | 14.64 ± 5.15 | 14.87 ± 2.93 | 0.53 | 0.13 | 1.166 | 1.750 | 1.66 | 6.84 | 98.1 |
| 2 | 2,3-Dihydroxybenzaldehyde | 10.00 ± 1.24 | 17.19 ± 0.31 | 0.20 | 0.81 | 1 | 1.125 | 1.53 | 7.97 | 97.9 |
| 3 | 4-Methylcatechol | 9.35 ± 1.14 | 18.83 ± 1.17 | 0.22 | 1.08 | 0.971 | 1.275 | 1.37 | 9.69 | 102.5 |
| 4 | Tetrachlorocatechol | 8.33 ± 1.02 | 9.93 ± 1.02 | 0.54 | 0.35 | 0.921 | 0.997 | 4.29 | 5.68 | 134.0 |
| 5 | Tyrphostine A23 | 7.90 ± 0.75 | 11.67 ± 0.98 | 0.02 | 0.65 | 0.898 | 1.067 | 1.16 | 7.24 | 130.3 |
| 6 | Octylgallate | 7.13 ± 1.57 | 9.32 ± 1.90 | 0.85 | 0.08 | 0.853 | 0.969 | 3.66 | 7.82 | 238.1 |
| 7 | 3-Fluorocatechol | 5.05 ± 0.57 | 11.70 ± 1.12 | 0.16 | 1.07 | 0.703 | 1.068 | 1.23 | 8.35 | 90.5 |
| 8 | Ethyl-3,4-dihydroxybenzylidenecyanoacetate | 4.40 ± 1.51 | 13.03 ± 4.12 | 0.24 | 0.01 | 0.643 | 1.115 | 2.09 | 8.67 | 173.4 |
| 9 | 2-Hydroxyestrone | 3.62 ± 1.17 | 7.73 ± 1.85 | N.D. | N.D. | 0.559 | 0.888 | 2.95 | 9.90 | 230.5 |
| 10 | Pyrogallol | 3.43 ± 1.15 | 5.91 ± 1.74 | 0.03 | 0.07 | 0.535 | 0.772 | 0.97 | 9.12 | 84.7 |
| 11 | Catechol | 3.24 ± 0.91 | 12.65 ± 4.68 | 0.05 | 0.13 | 0.511 | 1.102 | 0.88 | 9.50 | 86.2 |
| 12 | Dobutamine | 3.09 ± 0.74 | 4.52 ± 0.61 | 0.21 | N.D. | 0.490 | 0.655 | 3.47 | 9.65 | 253.4 |
| 13 | 2-(1-Thienyl)-ethyl-3,4-dihydroxybenzylidenecyanoacetate | 2.88 ± 2.68 | 3.14 ± 0.78 | 0.20 | 0.03 | 0.459 | 0.497 | 3.61 | 8.67 | 223.6 |
| 14 | 4-tert-Butyl-5-metoxycatechol | 2.66 ± 0.24 | 5.74 ± 0.86 | 1.16 | 0.04 | 0.425 | 0.759 | 3.02 | 9.59 | 176.9 |
| 15 | 2-Hydroxyestradiol | 2.49 ± 0.96 | 1.11 ± 0.10 | N.D. | N.D. | 0.396 | 0.045 | 3.46 | 10.14 | 231.0 |
| 16 | Methylgallate | 1.34 ± 0.21 | 3.40 ± 0.70 | 0.23 | 0.01 | 0.127 | 0.531 | 0.86 | 7.90 | 122.6 |
| 17 | 4-tert-Butylcatechol | 0.90 ± 0.01 | 2.25 ± 0.46 | 0.84 | 0.11 | −0.046 | 0.352 | 2.94 | 9.66 | 152.9 |
| 18 | Tolcapone | 0.87 ± 0.68 | 0.87 ± 0.68 | 0.04 | N.D. | −0.060 | −0.210 | 3.13 | 4.78 | 192.5 |
| 19 | Apomorphine | 0.78 ± 0.31 | 3.64 ± 0.83 | 0.02 | N.D. | −0.108 | 0.561 | 2.78 | 9.41 | 205.6 |
| 20 | Nitecapone | 0.65 ± 0.07 | 0.65 ± 0.07 | 0.06 | 0.02 | −0.187 | −0.110 | 1.04 | 4.60 | 182.6 |
| 21 | Epicatechin gallate | 0.64 ± 0.12 | 9.26 ± 0.77 | N.D. | 0.05 | −0.194 | 0.967 | 2.62 | 8.39 | 244.4 |
| 22 | 3,5-Dinitrocatechol | 0.61 ± 0.43 | 8.55 ± 2.81 | N.D. | 0.14 | −0.215 | 0.932 | 1.25 | 3.85 | 109.9 |
| 23 | Carbidopa | 0.52 ± 0.30 | 1.34 ± 0.05 | N.D. | N.D. | −0.284 | 0.127 | −0.13 | 9.94 | 159.2 |
| 24 | Epigallocatechin | 0.13 ± 0.16 | 0.98 ± 0.33 | 0.01 | 0.06 | −0.357 | −0.010 | 1.12 | 8.99 | 180.6 |
| 25 | Dihydrexidine | 0.37 ± 0.20 | 0.32 ± 0.05 | N.D. | N.D. | −0.432 | −0.490 | 2.64 | 9.94 | 210.9 |
| 26 | 4-Hydroxyestradiol | 0.28 ± 0.15 | 4.12 ± 1.58 | 0.02 | N.D. | −0.553 | 0.615 | 3.46 | 10.21 | 231.0 |
| 27 | Entacapone | 0.20 ± 0.17 | 0.20 ± 0.17 | 0.01 | 0.01 | −0.699 | −0.130 | 2.22 | 4.50 | 219.2 |
| 28 | Catechin | 0.13 ± 0.10 | 1.85 ± 0.60 | N.D. | N.D. | −0.886 | 0.267 | 0.51 | 9.56 | 182.2 |
| 29 | Epigallocatechin gallate | 0.13 ± 0.16 | 1.55 ± 0.13 | 0.01 | 0.06 | −0.886 | 0.190 | 2.56 | 8.38 | 241.2 |
| 30 | Epicatechin | 0.12 ± 0.09 | 2.21 ± 1.02 | 0.07 | N.D. | −0.921 | 0.344 | 0.51 | 9.56 | 182.1 |
| 31 | 6-Hydroxydopa | 0.10 ± 0.03 | 0.61 ± 0.10 | N.D. | N.D. | 1 | −0.210 | −2.72 | 10.00 | 132.7 |
| 32 | 6-Hydroxydopamine | 0.09 ± 0.08 | 0.08 ± 0.09 | N.D. | N.D. | −1.046 | −1.100 | −0.10 | 9.53 | 121.1 |
| 33 | Adrenaline | 0.07 ± 0.07 | 0.39 ± 0.53 | N.D. | N.D. | −1.155 | −0.410 | −0.70 | 9.60 | 142.6 |
| 34 | Dopamine | 0.06 ± 0.10 | 0.01 ± 0.02 | N.D. | N.D. | −1.222 | −2 | −0.98 | 9.41 | 122.7 |
| 35 | 3,4-Dihydroxymandelic acid | 0.06 ± 0.02 | 0.17 ± 0.12 | N.D. | N.D. | −1.222 | −0.770 | −0.39 | 9.66 | 111.9 |
| 36 | 3,4-Dihydroxybenzoic acid | 0.02 ± 0.01 | 0.01 ± 0.02 | N.D. | N.D. | −1.398 | −0.550 | 0.86 | 9.10 | 98.8 |
| 37 | 3,4-Dihydroxyphenyl acetic acid | 0.03 ± 0.05 | N.D. | N.D. | N.D. | −1.523 | −2 | 0.98 | 9.84 | 113.7 |
| 38 | Gallic acid | 0.03 ± 0.02 | 0.01 ± 0.02 | N.D. | N.D. | −1.523 | −2 | 0.70 | 8.95 | 97.2 |
| 39 | 5-Hydroxydopamine | 0.03 ± 0.02 | 0.16 ± 0.04 | N.D. | N.D. | −1.523 | −0.800 | 0.32 | 8.90 | 121.2 |
| 40 | 2,3-Dihydroxybenzoic acid | 0.02 ± 0.01 | 0.01 ± 0.01 | N.D. | N.D. | −1.699 | −2 | 1.2 | 10.11 | 98.8 |
| 41 | Noradrenaline | N.D. | 0.01 ± 0.01 | N.D. | N.D. | −2 | −2 | −1.24 | 9.57 | 121.0 |
| 42 | l-Dopa | N.D. | N.D. | N.D. | N.D. | −2 | −2 | −2.74 | 9.87 | 132.4 |
Glucuronidation activity was measured by liver microsomes of non-treated (RLM) and 3-MC-induced (RLM-3MC) rats. Values are expressed as nanomoles per minute per milligram of protein (±S.D.;n = 3 rats). Glucuronidation activity by the rat liver recombinant UGT2B1 and UGT1A6 was measured and expressed as nanomoles per minute per milligram of protein. The steric and electronic descriptors are described under Materials and Methods.Compounds are listed as numbers (No) according to a decreasing ranking order of their glucuronidation rate with liver microsomes of non-treated rats.
N.D., not detectable (0.01 nmol/min/mg of protein).