Table 4.
Molecular docking (blind and defined modes) of Breastin constituents to the Vinca alkaloid, taxane-, and colchicine-binding sites of β-tubulin. Shown are the lowest binding energies (LBEs, kcal/mol), predicted inhibition constants (pKi, µM), and amino acids involved in ligand interaction with β-tubulin. Vinorelbine, paclitaxel, colchicine, and nocodazole served as control compounds.
| Tubulin Binding Sites | Compounds | LBE (kcal/mol) | pKi (µM) | Amino Acids Involved in Ligand Interaction |
|---|---|---|---|---|
| Blind docking | Vinorelbine | −10.28 ± 0.46 | 0.04 ± 0.03 | HIS197, SER198, ASP199, VAL260, PRO263 |
| Paclitaxel | −9.45 ± 0.08 | 0.12 ± 0.02 | GLN256, THR257, VAL260, PRO261, ALA314, CYS347 | |
| Colchicine | −6.82 ± 1.01 | 22.58 ± 15.61 | ASP199, PRO263, HIS406, TRP407 | |
| Nocodazole | −6.31 ± 0.11 | 23.65 ± 4.43 | THR382, ALA385, ALA426, GLU429, GLU433 | |
| Adynerin | −8.52 ± 0.16 | 0.59 ± 0.16 | CYS12, THR145, VAL171, SER174, GLU183, ASP205, ASN206 | |
| Neritaloside | −8.80 ± 0.28 | 0.40 ± 0.19 | LYS163, LEU195, GLN256, VAL260, PRO263, HIS266 | |
| Oleandrin | −8.42 ± 0.04 | 0.67 ± 0.04 | LYS163, GLU196, ASP199, THR257, VAL260, PRO263, HIS266 | |
| Vanderoside | −8.66 ± 0.02 | 0.45 ± 0.01 | GLN11, CYS12, GLN15, SER140, VAL171, SER174, GLU183, ASP205, ASN206, TYR 224 | |
| Odoroside A | −8.15 ± 0.02 | 1.06 ± 0.04 | VAL23, LEU217, HIS229, ALA233, SER236, THR276, ARG320, PRO360, LEU371 | |
| Odoroside H | −8.06 ± 0.18 | 1.29 ± 0.36 | GLN11, CYS12, GLU71, ASP205 | |
| Vinca alkaloid-binding site (defined docking) | Vinorelbine | −10.86 ± 0.39 | 0.01 ± 0.00 | CYS12, SER140, LEU141, GLY142, VAL171, SER174, VAL177, SER178, ASP179, GLU183, ILE204, ASN206, TYR224 |
| Adynerin | −8.91 ± 0.15 | 0.37 ± 0.09 | CYS12, ALA99, SER140, VAL171, SER178, ASP179 | |
| Neritaloside | −9.75 ± 0.23 | 0.05 ± 0.03 | GLN11, CYS12, PRO173, SER174, GLU183, ASN206, TYR210, TYR224 | |
| Oleandrin | −8.73 ± 0.53 | 1.10 ± 0.79 | LYS176, VAL177, TYR210, ASP211, PHE214, PRO222, TYR224 | |
| Vanderoside | −9.87 ± <0.01 | 0.04 ± 0.00 | CYS12, GLN15, SER140, VAL171, PRO173, SER174, GLU183, ASP205, ASN206, TYR224, GLY225 | |
| Odoroside A | −9.15 ± 0.05 | 0.17 ± 0.02 | CYS12, ALA99, ASN101, THR145, VAL171, SER174, ASN206, GLU207 | |
| Odoroside H | −9.08 ± 0.04 | 0.29 ± 0.02 | CYS12, GLU71, ASN101, THR145, VAL171, SER174 | |
| Taxane-binding site (defined docking) | Paclitaxel | −9.93 ± 0.29 | 0.14 ± 0.11 | LEU217, HIS229, ALA233, PHE272, THR276, PRO360, ARG369, LEU371 |
| Adynerin | −8.02 ± 0.03 | 1.93 ± 0.03 | LEU217, LEU275, THR276, LEU286, LEU371 | |
| Neritaloside | −8.19 ± 0.11 | 1.02 ± 0.17 | LEU275, GLN281, GLY370, LEU371 | |
| Oleandrin | −8.50 ± 0.21 | 0.63 ± 0.21 | LEU217, THR276, LEU286, LEU 371, MET373 | |
| Vanderoside | −7.92 ± 0.07 | 1.61 ± 0.19 | VAL23, LEU217, HIS229, ALA233, SER277, ARG278, ARG320, PRO360, LEU371 | |
| Odoroside A | −8.14 ± 0.08 | 2.91 ± 0.69 | LEU217, LEU275, GLN281, LEU371, LYS372 | |
| Odoroside H | −8.36 ± 0.11 | 1.47 ± 0.84 | HIS229, GLN281, GLY370, LEU371, LYS372 | |
| Colchicine-binding site (blind docking) | Colchicine | −7.57 ± 0.01 | 2.83 ± 0.04 | ASP69, THR145, ALA180, TRY224, LEU248, LYS254 |
| Adynerin | −6.77 ± 0.05 | 10.91 ± 0.91 | GLY10, ALA99, SER178, ALA180, LEU248, LYS254 | |
| Neritaloside | −5.80 ± 0.14 | 57.77 ± 13.31 | LEU70, GLU71, ALA99, VAL177, THR179, ALA180, GLU183, ASN206, TYR224, LEU248 | |
| Oleandrin | −5.26 ± 0.14 | 144.33 ± 31.57 | ALA12, GLU71, ALA99, PRO173, VAL177, ALA180, GLU183, ASN206, TYR210, TYR224, LEU248, LYS254, ASP329 | |
| Vanderoside | −5.51 ± 0.22 | 98.22 ± 33.98 | GLN11, ASP69, LEU70, GLU71, VAL74, ASP98, TYR210, LEU248, LYS254, ASP329 | |
| Odoroside A | −8.19 ± 0.12 | 1.02 ± 0.20 | GLN11, LEU70, GLU71, ALA99, THR145, ALA180, GLU183, TYR224, LEU248 | |
| Odoroside H | −6.68 ± 0.08 | 12.90 ± 1.60 | GLN11, LEU70, GLU71, ALA99, THR179, ALA180, TYR210, TYR224, LEU248, LYS254, ASP329 |