Table 3.
Binding energy and nonbonding interaction of mitoxantrone and its derivatives.
| Compound | Docking against human topoisomerase II alpha (TOP2A) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Binding energy (kcal mol−1) | H-bond | Halogen bond | Hydrophobic interaction | Electrostatic interaction | |||||
| Amino acid-ligand atom | Distance (Å) | Amino acid-ligand atom | Distance (Å) | Amino acid-ligand atom | Distance (Å) | Amino acid-ligand atom | Distance (Å) | ||
| Mitoxantrone (D) | −9.2 | Lys723 [N-H⋯O] Ile856 [C-O⋯H]∗ Asp710 [C-O⋯H]∗ Ile856 [C-O⋯H]∗ Asp710 [C-O⋯H]∗ |
2.2693 3.0872 2.9119 3.0135 2.2831 |
Lys723 [alkyl-pi] Lys723 [alkyl-pi] |
4.8912 4.8521 |
||||
|
| |||||||||
| D1 | −9.5 | Glu712 [C-O⋯H] Glu839 [C-O⋯H]∗ His1005 [C-O⋯H]∗ Val1006 [C-O⋯H]∗ Glu839 [C-O⋯H]∗ His1005 [C-O⋯H]∗ Glu712 [C-O⋯H ]∗ |
2.8309 2.4579 2.8559 2.1817 2.7366 2.7720 2.6202 |
Ile715 [C-O⋯F] | 3.6260 | Phe1003 [pi-pi staked] | 4.7087 | Glu839 [anion-pi] | 3.9962 |
|
| |||||||||
| D2 | −9.4 | Lys723 [N-H⋯O] Asp710 [C-H⋯O]∗ Asp710 [C-H⋯O]∗ |
2.2143 2.9100 2.2783 |
Lys723 [alkyl-pi] Lys723 [alkyl-pi] |
4.8686 4.8569 |
||||
|
| |||||||||
| D3 | −9.8 | Ser709 [C-H⋯N]∗
Ser756 [C-H⋯Cl]∗ Asp545 [C-O⋯H]∗ His759 [N⋯H]∗ Glu839 [C-O⋯H]∗ Gln544 [C-O⋯H]∗ |
2.3741 2.8450 2.9559 2.6541 2.1800 2.2268 |
Val836 [alkyl-Cl] Pro724 [alkyl-pi] Val836 [alkyl-pi] His758 [pi-Cl] |
4.5719 4.5000 5.2539 5.3149 |
Lys728 [cation-pi] Asp831 [anion-pi] |
2.2629 3.5500 |
||
|
| |||||||||
| D4 | −10.3 | Asn770 [N-H⋯O] Asn779 [C-O⋯H-O] Ile856 [C-O⋯H]∗ Ile856 [C-O⋯H]∗ Asp710 [C-O⋯H]∗ Ile856 [C-O⋯H]∗ |
2.3508 2.4357 2.9606 3.0344 2.5335 2.4966 |
Lys723 [sigma-pi] Lys723 [alkyl-pi] |
2.7069 4.9847 |
Lys723 [cation-pi] | 2.7975 | ||
|
| |||||||||
| D5 | −9.3 | Lys723 [N-H⋯O] Ile856 [C-O⋯H]∗ Asp710 [C-O⋯H]∗ Ile856 [C-O⋯H]∗ Asp710 [C-O⋯H]∗ |
2.0085 2.9432 2.8721 2.9262 2.3241 |
Lys723 [alkyl-pi] Lys723 [alkyl-pi] Tyr757 [pi-Br] |
4.6518 4.9056 4.8900 |
||||
|
| |||||||||
| D6 | −9.9 | Asn770 [C-O⋯H-N] Asn770 [O⋯H-N] Gly852 [C-O⋯H-O] Ile856 [C-O⋯H]∗ Asn710 [C-O⋯H]∗ Ile856 [C-O⋯H]∗ |
2.3828 2.6450 2.7306 2.8943 2.4152 2.6609 |
Lys723 [sigma-pi] Lys723 [alkyl-pi] |
2.6360 5.1763 |
Lys723 [cation-pi] Lys723 [cation-pi] |
3.5014 2.9085 |
||
|
| |||||||||
| D7 | −9.5 | Glu839 [C-O⋯H-N] Val1006 [C-O⋯H-N] Ser717 [O⋯H] Glu839 [C-O⋯H]∗ Val1006 [C-O⋯H]∗ His1005 [C-O⋯H]∗ |
3.0102 2.9825 2.6782 2.7621 2.2233 3.0479 |
Phe1003 [pi-pi stacked] Pro724 [alkyl-I] Phe1003 [pi-I] |
5.0840 4.6167 4.7419 |
Glu839 [anion-pi] | 3.7952 | ||
|
| |||||||||
| D8 | −9.7 | Asn770 [C-O⋯H-N] Asn770 [O⋯H-N] Gly852 [C-O⋯H] Ile856 [C-O⋯H]∗ Asn710 [C-O⋯H]∗ Ile856 [C-O⋯H]∗ |
2.3318 2.3759 2.8141 2.8758 2.6189 2.4101 |
Lys723 [alkyl-pi] Lys723 [alkyl-pi] |
4.2645 5.3858 |
Lys723 [cation-pi] Lys723 [cation-pi] |
3.5624 2.7612 |
||
|
| |||||||||
| D9 | −10.3 | Lys723 [N-H⋯O-C] Ile856 [C-O⋯H]∗ Asp710 [C-O⋯H]∗ Ile856 [C-O⋯H]∗ Asp710 [C-O⋯H]∗ |
2.0587 2.9275 2.9210 2.8580 2.3996 |
Gly725 [N-H⋯F] Gly725 [N-H⋯F] Gly725 [C-H⋯F] |
2.9348 2.6339 2.2421 |
Tyr757 [pi-alkyl] Lys723 [alkyl-pi] Lys723 [alkyl-pi] |
5.1734 4.7419 4.9257 |
||
|
| |||||||||
| D10 | −10.0 | Arg713 [N-H⋯O-C] Arg713 [N-H⋯O] Lys723 [N-H⋯F] Ser763 [C-O⋯N] Arg929 [N-H⋯O] Arg929 [N-H⋯O] His759 [C-O⋯H]∗ |
2.4985 2.3481 2.2497 2.4413 2.9278 2.8935 2.8837 |
Arg713 [C-O⋯F] | 3.3749 | Lys723 [alkyl-alkyl] Lys723 [alky-pi] Ille856 [alkyl-pi] |
4.2984 5.4568 5.0991 |
||
∗Nonconventional hydrogen bond.