Table 2.
Virtual screening affinity predictions (Kd and ΔGbind) for the top-ranked and the experimentally tested flavonoid compounds, and the respective biological activities.
| Virtual Screening a | Biological Activity b | ||||
|---|---|---|---|---|---|
| Ranking | Compound | Kd (nM) | ΔGbind (kcal/mol) | % Accumulation (10 µM) | % Accumulation (20 µM) |
| 1 | 25 | 1.16 | −7.7 | n.d. | n.d. |
| 2 | 37 | 1.27 | −9.0 | n.d. | n.d. |
| … | … | ||||
| 14 | 10 | 3.49 | −9.5 | 111.2 ± 12.0 | 142.5 ± 30.2 |
| 15 | 3 | 3.80 | −9.9 | 102.3 ± 4.2 | 111.3 ± 11.0 |
| 25 | 4 | 9.62 | −8.2 | 95.5 ± 8.5 | 90.9 ± 8.9 |
| 31 | 7 | 14.3 | −10.1 | 122.3 ± 23.4 | 129.5 ± 17.6 |
| 32 | 5 | 15.3 | −9.4 | 112.5 ± 23.1 | 114.5 ± 9.4 |
| 33 | 1 | 16.8 | −9.5 | 97.3 ± 4.3 | 107.9 ± 10.1 |
| 34 | 2 | 17.8 | −9.3 | 97.3 ± 3.7 | 99.7 ± 9.1 |
| 40 | 9 | 26.0 | −9.4 | 105.9 ± 3.7 | 129.6 ± 31.9 |
| 42 | 8 | 28.4 | −9.4 | 106.7 ± 13.1 | 115.3 ± 23.0 |
| 44 | 6 | 36.6 | −9.9 | 119.3 ± 22.9 | 127.2 ± 17.6 |
| Best lignan c | Lig-(+)-4 | 17.5 | −7.6 | n.d. | 283 ± 33 (Lig-1) d |
| Worst lignan c | Lig-11 | 359.8 | −7.3 | n.d. | 125 ± 17 (Lig-11) d |
|
(R)-vera
(S)-vera |
0.74 0.46 |
−7.9 −7.3 |
137.7 ± 6.2 | 147.5 ± 7.7 239 ± 30 d |
|
a The compounds are ranked by the predicted Kd affinity scores (from NNscore) with cluster 5, while the respective ΔGbind (from AutoDock Vina) is presented for comparison; b intracellular doxorubicin accumulation (in %) in HL60/MDR cells is the mean value ± SD from at least four independent experiments performed in duplicate, after pretreatment with the flavonoids at a concentration of 10 µM and 20 µM; c for comparison, the best and worst results obtained in the training set of lignans and verapamil are presented (compound specified in brackets); d from ref. [24] with 25 µM of inhibitor instead of 20 µM. The significant biological activities are highlighted in bold; n.d. means “not determined”.