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Table 1 The list of TNFα, TNFR1 and TNFα-TNFR1 complex and their best lead molecules interactions, binding energies, smiles, bond angles, bond lengths and number of hydrogen bonds

From: Identification of novel inhibitors for TNFα, TNFR1 and TNFα-TNFR1 complex using pharmacophore-based approaches

TNF-α
Ids Popular name SMILES Binding energy (ΔG) kcal/mol−1 Protein and ligands H-bond interactions Angles (°) Distance (Å) No. of H-bonds
ZINC09609430 N-[1-(2,5-dioxabicyclo[4.4.0]deca-7,9,11-trien-8-yl)ethyl]-3-[7-(4-fluorophenyl)-2,4,8-trimethyl-1,5 Cc1c(c(n2c(n1)c(c(n2)C)c3ccc(cc3)F)C)CCC(=O)N[C@H](C)c4ccc5c(c4)OCCO5 − 9.2 Gly121 CH–HN 107.21 3.17 01
ZINC49467549 N-[2-[3-(4-methyl-2-phenyl-thiazol-5-yl)-6-oxo-pyridazin-1-yl]ethyl]-2-(1-naphthyloxy)acetamide Cc1c(sc(n1)c2ccccc2)c3ccc(=O)n(n3)CCNC(=O)COc4cccc5c4cccc5 − 9.0 Ile58, Leu120, Gly121 and Tyr151
ZINC13113075 (2R)-2-[[5-[(1S)-1-(4-fluorophenoxy)ethyl]-1,3,4-oxadiazol-2-yl]sulfanyl]-1-(2-methyl-1H-indol-3-yl) Cc1c(c2ccccc2[nH]1)C(=O)[C@@H](C)Sc3nnc(o3)[C@H](C)Oc4ccc(cc4)F − 8.8 Tyr151 CO–OC 98.29 3.29 01
ZINC39907639 2-[(3,4-dimethoxyphenyl)methyl]-1-[2-(1-naphthyloxy)ethyl]benzimidazole COc1ccc(cc1OC)Cc2nc3ccccc3n2CCOc4cccc5c4cccc5 − 8.5 Ile58, Leu120, Gly121 and Tyr151
ZINC25251930 1-[[(R)-(3-methoxyphenyl)-(1-methylimidazol-2-yl)methyl]amino]-3-methyl-pyrido[1,2-a]benzimidazole-4 cc1cc(n2c3ccccc3nc2c1C#N)N[C@H](c4cccc(c4)OC)c5nccn5C − 8.1 Ile58 CO–NC 3.16 17.87 03
Leu120 CO–NH 3.31 39.97  
Gly121 CN–OC 2.99 111.96  
307 (Query) 6,7-dimethyl-3-[(methyl{2-[methyl({1-[3-(trifluoro methyl)phenyl]-1H-indol-3-yl}methyl)amino]ethyl}amino)methyl]-4H-chromen-4-one Cn(ccn(c)cc1=c[n](c2=cc(=cc=c2)c(f)(f)f)c3=cc=cc=c13)cc4=coc5=cc(=c(c)c=c5c4=o)c − 6.8 Ile58, Leu120, Gly121 and Tyr151
TNFR1
Ids Popular name SMILES Binding energy (ΔG) kcal/mol−1 Protein and ligands H-bond interactions Angles (°) Distance (Å) No. of H-bonds
ZINC02968981 N-benzyl-2-[[2-(4-nitrophenyl)-[1, 2, 4]triazolo[1,5-c]quinazolin-5-yl]thio]acetamide c1ccc(cc1)CNC(=O)CSc2nc3ccccc3c4n2nc(n4)c5ccc(cc5)[N+](=O)[O–] − 10.1 Lys75 CO–ON
Gln82 CO–ON
Gln82 CN–ON
Arg104 CN–OC
Tyr106 CO–OC
112.42
97.99
101.92
109.87
149.80
3.25
3.35
3.16
2.84
3.20
05
ZINC09544246 2-[[5-(1H-indol-3-yl)-1,3,4-oxadiazol-2-yl]sulfanyl]-N-(3-sulfamoylphenyl)-acetamide c1ccc2c(c1)c(c[nH]2)c3nnc(o3)SCC(=O)Nc4cccc(c4)S(=O)(=O)N − 9.8 Glu56 CN–OC
Glu56 CO–NH
Ser57 CO–NH
Ser59 CO–OC
Cys70 CN–OC
Cys73 CO–NH
Ser74 CO–NH
167.25
106.92
119.86
124.31
109.30
150.85
105.01
2.93
2.06
3.34
2.90
3.06
3.24
3.19
07
ZINC58047088 N-[(4-fluorophenyl)methyl]-2-[(3-methyl-2-oxo-[1, 2, 4]triazino[2,3-c]quinazolin-6-yl)sulfanyl]acetami Cc1c(=O)nc2c3ccccc3nc(n2n1)SCC(=O)NCc4ccc(cc4)F − 9.5 Ser74 CO–NH
Asn110 CO–NH
131.62
123.93
3.07
3.01
02
ZINC72021182 2-(4-chlorobenzoyl)-N-[2-[(2-hydroxybenzoyl)amino]ethyl]benzamide c1ccc(c(c1)C(=O)c2ccc(cc2)Cl)C(=O)NCCNC(=O)c3ccccc3O − 9.3 Arg104 CN–OH 85.81 2.98 01
ZINC08704414 2-(methylBLAHyl)sulfanyl-N-(p-tolylmethyl)propanamide Cc1ccc(cc1)CNC(=O)[C@@H](C)Sc2nc3ccccc3c4n2nc(n4)C − 9.1 Ser74 CO–NH
Lys75 CO–NH
Arg77 CN–OC
Asn110 CO–NH
55.03
30.27
101.39
111.93
3.13
3.11
3.02
3.37
04
ZINC33832439 (query) 1-Hydroxy-3-methoxy-6-methyl-8-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)anthracene-9,10-dione Cc1cc2c(c(c1)O[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)O)O)C(=O)c4c(cc(cc4O)OC)C2=O − 7.6 Arg77 CN–OC
Cys96 CN-OH
Cys96 CO–OH
Arg104 CN—OH
Arg104 CN–OH
Arg104 CN—OH
Tyr106 CO–OH
Asn110 CO–OH
111.69
106.76
151.20
92.64
120.04
107.99
58.49
3.01
3.09
2.70
3.31
2.81
3.00
3.16
08
TNFα-TNFR1 complex
Ids Popular name SMILES Binding energy (ΔG) kcal/mol−1 Protein and ligands H-bond interactions Angles (°) Distance (Å) No. of H-bonds
ZINC05462670 Chaetochromin B C[C@@H]1[C@H](Oc2cc3c(c(cc(c3c4c5cc6c(c(c5c(cc4O)O)O)C(=O)[C@@H]([C@@H](O6)C)C)O)O)c(c2C1=O)O)C − 10.0 Ser74 CO–OH
Thr94 CO–OH
Glu109 CO–OC
Asn110 CO–OH
72.63
27.39
121.49
45.29
3.19
2.93
3.36
2.73
04
ZINC35681945 N2-[(2R)-2-(dimethylamino)-2-(2-methoxyphenyl)ethyl]-N4-(4-ethoxyphenyl)-5-nitro-pyrimidine-2,4,6-tr CCOc1ccc(cc1)Nc2c(c(nc(n2)NC[C@@H](c3ccccc3OC)[NH+](C)C)N)[N+](=O)[O–] − 9.7 Lys75 CO–NH
Gln82 CO–ON
Gln82 CN–ON
Asp93 CO–NH
Arg104 CN–OC
Asn110 CO–NH
76.93
114.27
111.31
155.37
95.38
129.41
3.32
3.08
3.38
2.89
3.20
2.79
06
ZINC23553920 6-[[4-allyl-5-(2-methoxyphenyl)-1,2,4-triazol-3-yl]sulfanylmethyl]-N′-(2-ethylphenyl)-1,3,5-triazine CCc1ccccc1Nc2nc(nc(n2)N)CSc3nnc(n3CC=C)c4ccccc4OC − 9.5 Ser74 CO–OC
Thr94 CO–NH
Thr94 CO–NH
75.40
46.06
52.19
3.49
3.12
3.20
03
ZINC05328058 DNC011371 C[C@H]1CC(=O)c2c(cc3c(c2O)c(cc(c3c4c5cc6c(c(c5c(cc4O)O)O)C(=O)C[C@@H](O6)C)O)O)O1 − 8.9 Ser74 CO–OH
Gln82 CO–OC
Pro90 CO–OH
Asn92 CN–OH
Cys96 CN–OH
49.49
103.84
73.92
29.76
65.40
2.80
3.48
3.24
2.97
2.95
05
ZINC17206695 (2Z)-2-(2,5-dimethoxyphenyl)imino-6-[(3R,5S)-3,5-dimethyl-1-piperidyl]-5-nitro-1H-pyrimidin-4-amine C[C@@H]1C[C@@H](CN(C1)c2c(c(nc(n2)Nc3cc(ccc3OC)OC)N)[N+](=O)[O–])C − 8.5 Ser74 CO–NH
Ser74 CO–NH
Asn93 CO–NH
Asn110 CN–ON
Asn110 CN–NO
Ser147 OC–OC
55.45
30.72
47.81
102.70
54.86
2.81
3.20
2.73
2.81
3.35
06
ZINC08214556 (query) Erythrosine sodium (USP) c1ccc2c(c1)C(=O)OC23c4cc(c(c(c4Oc5c3cc(c(c5I)O)I)I)O)I − 7.2 Thr94 CO–OC
Asn110 CN–OC
120.52
102.30
3.05
3.20
02