Table 6 The study examined the molecular docking interaction between synthesized compounds (3h and 4c), the most common antifungal target proteins (DHFR and NMT1), the standard drug (Fluconazole), and reference compounds (R64 and 18 H).
Comp. | Target protein | Binding energy (kcal/mol) | Estimated Ki | Most interacting amino acids | |||
|---|---|---|---|---|---|---|---|
Hydrogen bond (distance (Å)) | Van der Waals | π-σ interactions | Other interactions (π-π; π-alkyl; π-ion) | ||||
3h | DHFR | − 7.96 | 1.45 µM | ALA11 (1.96), TYR27 (1.96) | VAL10, GLY23, LEU29, THR58, SER61, ILE112, GLY113, GLY114, ALA115, TYR118 | MET25 | ILE19, ILE33, LYS57 |
NMT1 | − 8.24 | 915.49 nM | TYR335 (2.23) | ASP110, LEU350, LEU355, ASN392, CYS393, LEU415, VAL449, LEU450, LEU451 | ILE352, TYR354 | TYR225, HIS227, PHE240, PHE339, VAL390, LEU394 | |
4c | DHFR | − 8.44 | 646.91 nM | THR58 (1.91), GLY23 (3.27) | GLY20, GLU32, PHE36, SER61, ILE112, GLY113, GLY114, ALA115, THR147 | MET25 | ILE9, VAL10, ALA11, ILE19, LYS57, TYR118 |
NMT1 | − 8.76 | 381.92 nM | ASN392 (2.78) | HIS227, PHE339, LEU350, CYS393, LEU415, VAL449, LEU450, LEU451 | ILE352, LEU394 | TYR225, PHE240, TYR354, VAL390 | |
R64 | DHFR | − 8.09 | 1.17 µM | ALA11 (2.09), GLY114 (3.25), TYR118 (3.74) | ILE9, VAL10, TRP27, GLU32, THR58, LEU69, GLY113, ALA115 | ILE19, MET25 | ILE33, PHE36, ILE62, ILE112 |
NMT1 | − 10.60 | 16.88 nM | HIS227 (2.11), ASN392 (2.20), CYS393 (2.84), LEU450 (2.42) | ASP110, GLN226, TYR335, LEU350, LEU355, LEU415, LEU451 | ILE352, LEU394, | PHE115, PHE117, TYR225, PHE240, PHE339, TYR354, VAL390, VAL449 | |
18 H | DHFR | − 8.54 | 550.32 nM | ILE9 (2.08), GLU32 (1.87), ILE112 (2.05), | VLA10, LYS24, ILE33, TYR35, THR58, TYR118, THR133 | MET25 | ALA11, PHE36, ILE62, PRO63, LEU69 |
NMT1 | − 9.67 | 81.53 nM | GLU109 (3.49), TYR225 (2.28), TYR335 (2.06, 2.16), TYR354 (3.22), LEU450 (2.16), LEU451 (2.99) | ASP110, TYR335, VAL449, LEU350, PHE356, VAL390, ASN392, CYS393 | LEU394 | PHE117, HIS227, PHE240, PHE339, ILE352 | |
Fluconazole | DHFR | − 5.61 | 77.13 µM | TRP27 (2.10), GLU32 (2.05), TYR118 (2.38) | VAL10, ILE112, ILE135 | – | ILE9, ALA11, MET25, LEU29, ILE33, PHE36 |
NMT1 | − 6.10 | 33.72 µM | HIS227 (2.74), TYR354 (2.02), CYS393 (3.64) | ASP110, PHE117, GLN226, LEU350, ASN392, LEU394 | – | TYR225, PHE240, PHE339, ILE352, | |
