Table 3.
Comparison of measured and predicted inhibitory values for sulfonamide derivatives with a symmetric pair of amino acids.
| Name | Linker | Model | hCA I (KI, nM) | hCA II (KI, nM) | hCA IV (KI, nM) | hCA IX (KI, nM) | hCA II/IX | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Measured | Predicted | Measured | Predicted | Measured | Predicted | Measured | Predicted | Measured | Predicted | |||
| TSA Asp | 0 | Train | 8259.8 | 8257.0 | 6219.1 | 6201.2 | 10000.0 | 10000.0 | 211.1 | 135.0 | 29.5 | 45.9 |
| TSAM Asp | 1 | Train | 3700.0 | 3682.6 | 5953.7 | 5693.6 | 10000.0 | 9999.6 | 2364.1 | 2159.9 | 2.5 | 2.6 |
| TSAE Asp | 2 | Validation | 10000.0 | 9866.0 | 5519.6 | 5931.6 | 10000.0 | 10000.0 | 25.8 | 44.7 | 213.9 | 132.7 |
| TSA B-Ala | 0 | Train | 673.0 | 364.2 | 368.0 | 235.8 | 9596.0 | 9990.0 | 8.9 | 12.5 | 41.3 | 18.9 |
| TSAM B-Ala | 1 | Train | 655.4 | 309.4 | 661.6 | 239.6 | 4476.0 | 4519.5 | 1818.5 | 1395.9 | 0.4 | 0.2 |
| TSAE B-Ala | 2 | Train | 960.7 | 1396.7 | 892.1 | 752.2 | 10000.0 | 9999.8 | 134.2 | 8.5 | 6.6 | 88.7 |
| TSA Glu | 0 | Validation | 9260.8 | 8976.3 | 7125.0 | 6203.0 | 10000.0 | 9999.8 | 202.4 | 65.7 | 35.2 | 94.4 |
| TSAM Glu | 1 | Validation | 6214.1 | 7938.1 | 695.2 | 771.3 | 4125.8 | 5622.2 | 193.2 | 19.5 | 3.6 | 39.6 |
| TSAE Glu | 2 | Train | 10000.0 | 10035.4 | 2284.3 | 2269.0 | 10000.0 | 9910.8 | 27.1 | 28.3 | 84.3 | 80.3 |
| TSA Gly | 0 | Train | 4550.0 | 277.0 | 376.0 | 235.7 | 10000.0 | 9978.9 | 8.4 | 8.8 | 44.8 | 26.8 |
| TSAM Gly | 1 | Validation | 9362.4 | 5603.6 | 478.4 | 235.7 | 867.3 | 1651.2 | 145.8 | 10.5 | 3.3 | 22.4 |
| TSAE Gly | 2 | Train | 4023.8 | 4032.9 | 428.1 | 235.7 | 3415.2 | 3465.8 | 330.4 | 8.4 | 1.3 | 28.1 |
| TSA Ile | 0 | Train | 10000.0 | 9724.8 | 2948.9 | 2952.7 | 4021.2 | 4024.9 | 92.6 | 47.1 | 31.8 | 62.7 |
| TSAM Ile | 1 | Train | 664.5 | 914.8 | 628.5 | 807.6 | 76.3 | 154.9 | 164.3 | 22.1 | 3.8 | 36.5 |
| TSAE Ile | 2 | Train | 7337.2 | 7292.8 | 1556.2 | 1644.5 | 1421.3 | 1301.5 | 189.3 | 19.9 | 8.2 | 82.8 |
| TSA Leu | 0 | Train | 4191.9 | 4392.1 | 4528.8 | 4505.6 | 2380.9 | 2482.7 | 24.0 | 25.2 | 188.7 | 178.6 |
| TSAM Leu | 1 | Validation | 96.9 | 387.6 | 396.0 | 588.8 | 516.8 | 537.2 | 167.3 | 288.6 | 2.4 | 2.0 |
| TSAE Leu | 2 | Train | 4854.5 | 4960.0 | 912.5 | 511.3 | 367.1 | 171.1 | 123.8 | 32.0 | 7.4 | 16.0 |
| TSA Met | 0 | Train | 346.7 | 798.1 | 803.7 | 565.5 | 3294.0 | 3040.8 | 2222.2 | 1960.4 | 0.4 | 0.3 |
| TSAM Met | 1 | Train | 531.3 | 459.8 | 3170.6 | 3153.4 | 45.6 | 64.0 | 1274.9 | 1962.3 | 2.5 | 1.6 |
| TSAE Met | 2 | Validation | 4527.8 | 1988.3 | 5017.9 | 4957.6 | 2336.1 | 60.1 | 2592.4 | 1951.0 | 1.9 | 2.5 |
| TSA Phe | 0 | Train | 305.4 | 210.1 | 866.1 | 870.8 | 9387.0 | 9998.7 | 191.5 | 131.5 | 4.5 | 6.6 |
| TSAM Phe | 1 | Train | 67.1 | 364.1 | 235.7 | 394.3 | 61.9 | 47.9 | 119.6 | 107.9 | 2.0 | 3.7 |
| TSAE Phe | 2 | Train | 4893.8 | 4847.3 | 6161.8 | 5956.5 | 374.5 | 47.5 | 223.1 | 22.9 | 27.6 | 259.8 |
| TSA Pro | 0 | Validation | 87.0 | 188.4 | 3112.8 | 3168.2 | 9315.0 | 8607.2 | 295.0 | 56.1 | 10.6 | 56.4 |
| TSAM Pro | 1 | Train | 256.4 | 204.1 | 773.1 | 759.2 | 350.4 | 329.7 | 265.5 | 158.4 | 2.9 | 4.8 |
| TSAE Pro | 2 | Validation | 958.4 | 398.8 | 1070.8 | 667.0 | 2206.9 | 719.9 | 25.7 | 47.9 | 41.7 | 13.9 |
| TSA Val | 0 | Train | 398.7 | 498.5 | 5335.4 | 5503.5 | 10000.0 | 9942.7 | 2111.1 | 2241.1 | 2.5 | 2.5 |
| TSAM Val | 1 | Validation | 377.0 | 308.8 | 839.3 | 1050.1 | 656.8 | 418.9 | 1371.8 | 457.2 | 0.6 | 2.3 |
| TSAE Val | 2 | Train | 932.2 | 613.9 | 804.1 | 857.2 | 476.3 | 677.7 | 130.9 | 179.2 | 6.1 | 4.8 |
Validation was used for experimental determination of inhibition data and calculations of predicted values were made by using artificial neural networks. TSA = triazinyl-aminobenzenesulfonamide; TSAM = triazinyl-aminomethylbenzenesulfonamide; TSAE = triazinyl-aminoethylbenzenesulfonamide; 0 = amino; 1 = aminomethyl; 2 = aminoethyl.