Scheme 1.
Protocol synthesis of compounds 2–4.
Scheme 1.
Protocol synthesis of compounds 2–4.
Scheme 2.
Plausible reaction mechanism for the formation of the 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4.
Scheme 2.
Plausible reaction mechanism for the formation of the 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4.
Figure 1.
Optimized structure of the reagent and the product (2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4) B3LYP/6-31+G(d).
Figure 1.
Optimized structure of the reagent and the product (2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4) B3LYP/6-31+G(d).
Figure 2.
Scan calculations of the product as a function of dihedral angle.
Figure 2.
Scan calculations of the product as a function of dihedral angle.
Figure 3.
Molecular Orbitals MOs (HOMO and LUMO) of the desired product.
Figure 3.
Molecular Orbitals MOs (HOMO and LUMO) of the desired product.
Figure 4.
(a) Proposed tautomeric equilibrium for compound 3; (b) optimized TSs, amine and alcohol tautomers at DFT B3LYP/6-31+G(d) level of theory.
Figure 4.
(a) Proposed tautomeric equilibrium for compound 3; (b) optimized TSs, amine and alcohol tautomers at DFT B3LYP/6-31+G(d) level of theory.
Figure 5.
IRC plot of the tautomeric equilibrium.
Figure 5.
IRC plot of the tautomeric equilibrium.
Figure 6.
Computed UV-abs spectra at TD-DFT B3LYP/6-31+G(d) level as a function of several solvents.
Figure 6.
Computed UV-abs spectra at TD-DFT B3LYP/6-31+G(d) level as a function of several solvents.
Figure 7.
Computed UV-emission spectra at TD-DFT B3LYP/6-31+G(d) level as afunction of several solvents.
Figure 7.
Computed UV-emission spectra at TD-DFT B3LYP/6-31+G(d) level as afunction of several solvents.
Figure 8.
Absorption spectra of 2 × 10−6 M coumarin 4 in different solvents.
Figure 8.
Absorption spectra of 2 × 10−6 M coumarin 4 in different solvents.
Figure 9.
Normalized emission spectra of 7.6 × 10
−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4 in
CCl
4,
n-heptane,
ethanol,
CHCl
3,
THF,
formamide.
Figure 9.
Normalized emission spectra of 7.6 × 10
−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4 in
CCl
4,
n-heptane,
ethanol,
CHCl
3,
THF,
formamide.
Figure 10.
Effect of solvent relative polarity on λem max of 7.6 × 10−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4.
Figure 10.
Effect of solvent relative polarity on λem max of 7.6 × 10−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4.
Figure 11.
Absorption spectra of 9.2 × 10
−6 M coumarin
4 in
THF,
CH
3CN, and
CHCl
3.
Figure 11.
Absorption spectra of 9.2 × 10
−6 M coumarin
4 in
THF,
CH
3CN, and
CHCl
3.
Figure 12.
Effect of solvent relative polarity on λab max of 7.6 × 10−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4.
Figure 12.
Effect of solvent relative polarity on λab max of 7.6 × 10−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4.
Figure 13.
Absorption spectra of 9.2 × 10
−6 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4. in
CH
3CN and
CCl
4 solvents.
Figure 13.
Absorption spectra of 9.2 × 10
−6 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4. in
CH
3CN and
CCl
4 solvents.
Figure 14.
Absorption spectra of 9.2 × 10
−6 M in
CHCl
3,
ethanol and
6.8 × 10
−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4-doped PVA thin film, thickness 100 μm (λ
ab max at 243, 307 nm, λ
ab max at 238, 307 nm and λ
ab max at 238, 307 nm, respectively).
Figure 14.
Absorption spectra of 9.2 × 10
−6 M in
CHCl
3,
ethanol and
6.8 × 10
−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4-doped PVA thin film, thickness 100 μm (λ
ab max at 243, 307 nm, λ
ab max at 238, 307 nm and λ
ab max at 238, 307 nm, respectively).
Figure 15.
Effect of solvent relative polarity on Stokes shift (nm) of 7.6 × 10−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4.
Figure 15.
Effect of solvent relative polarity on Stokes shift (nm) of 7.6 × 10−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4.
Figure 16.
Fluorescence spectra of 6.2 × 10
−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4 in
toluene,
CHCl
3,
ethanol,
pentanol and
formamide, λ
ex = 376 nm.
Figure 16.
Fluorescence spectra of 6.2 × 10
−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4 in
toluene,
CHCl
3,
ethanol,
pentanol and
formamide, λ
ex = 376 nm.
Figure 17.
Variation of the fluorescence quantum yield ɸf with the solvent polarity.
Figure 17.
Variation of the fluorescence quantum yield ɸf with the solvent polarity.
Figure 18.
Fluorescence spectra of 6.2 × 10
−4 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4 in toluene
fresh and
irradiated for 71 min, λ
ex = 376 nm.
Figure 18.
Fluorescence spectra of 6.2 × 10
−4 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4 in toluene
fresh and
irradiated for 71 min, λ
ex = 376 nm.
Figure 19.
Normalized absorption spectra of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4 6.8 × 10
−5 M in CH
3CN,
fresh,
alkalized using NaOH, and
acidified using H
2SO
4.
Figure 19.
Normalized absorption spectra of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4 6.8 × 10
−5 M in CH
3CN,
fresh,
alkalized using NaOH, and
acidified using H
2SO
4.
Figure 20.
Normalized fluorescence spectra of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4 6.8 × 10
−5 M in CH
3CN λ
ex = 304 nm,
fresh λ
em, max 406 nm, alkalized usingNaOH
λ
em, max 404 nm, and acidified using H
2SO
4 λ
em, max 387 nm.
Figure 20.
Normalized fluorescence spectra of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile
4 6.8 × 10
−5 M in CH
3CN λ
ex = 304 nm,
fresh λ
em, max 406 nm, alkalized usingNaOH
λ
em, max 404 nm, and acidified using H
2SO
4 λ
em, max 387 nm.
Figure 21.
Fluorescence spectra of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4 in ETOH increase in emission intensities at increasing concentration.
Figure 21.
Fluorescence spectra of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4 in ETOH increase in emission intensities at increasing concentration.
Figure 22.
Fluorescence spectra of 7.5 × 10−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4; decrease in emission intensity at increasing [Cu2+]: 0, 2, 4, 6, 8, 10, 15, 20, 25 μM, = 376 nm.
Figure 22.
Fluorescence spectra of 7.5 × 10−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4; decrease in emission intensity at increasing [Cu2+]: 0, 2, 4, 6, 8, 10, 15, 20, 25 μM, = 376 nm.
Figure 23.
Fluorescence spectra of 7.5 × 10−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4 in an aqueous solvent; decrease in emission intensity at increasing [Ni2+]: 0, 2, 4, 6, 8, 10, 12 μM, = 376 nm.
Figure 23.
Fluorescence spectra of 7.5 × 10−5 M of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4 in an aqueous solvent; decrease in emission intensity at increasing [Ni2+]: 0, 2, 4, 6, 8, 10, 12 μM, = 376 nm.
Figure 24.
Stern–Volmer plot of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4 with increasing concentrations of Cu2+.
Figure 24.
Stern–Volmer plot of 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4 with increasing concentrations of Cu2+.
Table 1.
Computed activation energy () and free energy of reaction values () (in kcal·mol−1) of the studied tautomeric equilibrium as a function of solvation model.
Table 1.
Computed activation energy () and free energy of reaction values () (in kcal·mol−1) of the studied tautomeric equilibrium as a function of solvation model.
Reaction Medium | | |
Gas phase | 36.00 | −6.86 |
Explicit model | 14.18 | −1.65 |
Implicit model | 35.87 | −7.72 |
Table 2.
Computed MEP surface and maximum and minimum potential values (in kcal·mol−1) of reagent at B3LYP/6-31+G(d).
Table 2.
Computed MEP surface and maximum and minimum potential values (in kcal·mol−1) of reagent at B3LYP/6-31+G(d).
|
---|
Site | | |
---|
C8 | | −20.71 |
O11 | | −8.38 |
O12 | | −31.38 |
C13 | 8.60 | |
H18 | 10.04 | |
H20 | 5.44 | |
H21 | 14.12 | |
H22 | 2.61 | |
O23 | | −23.33 |
Table 3.
Computed maximum and minimum potential values (in kcal·mol−1) of the product at B3LYP/6-31+G(d).
Table 3.
Computed maximum and minimum potential values (in kcal·mol−1) of the product at B3LYP/6-31+G(d).
|
---|
Site | | |
---|
C8 | 17.18 | |
O10 | 16.47 | |
O12 | | −28.29 |
N14 | 15.49 | |
C15 | 4.72 | |
O19 | | −42.57 |
C22 | 1.60 | |
O26 | | −11.28 |
C27 | 2.55 | |
N28 | | −37.98 |
H33 | 33.29 | |
H34 | 11.43 | |
H40 | 47.24 | |
Table 4.
Computed optical characteristics (wavelength (, nm); lowest-energy dipole-allowed excited states (, eV); the MOs transitions (major contributions,%); molar absorption coefficient (ε(, L·mol−1·cm−1)); and the oscillator strength of the maximum wavelength at TD-DFT B3LYP/6-31+G(d) as a function of several solvents.
Table 4.
Computed optical characteristics (wavelength (, nm); lowest-energy dipole-allowed excited states (, eV); the MOs transitions (major contributions,%); molar absorption coefficient (ε(, L·mol−1·cm−1)); and the oscillator strength of the maximum wavelength at TD-DFT B3LYP/6-31+G(d) as a function of several solvents.
Solvent | | | (%) | ε() | |
---|
THF | 309 | 3.21 | H→L (58%) | 26,736 | 0.65 |
3.24 | H-1→L (57%) |
249 | 3.80 | H-2→L (94%) | - | - |
4.04 | H-1→L + 1 (66%) |
4.10 | H-4→L (62%) |
202 | 4.60 | H-2→L + 1 (88%) | - | - |
4.71 | H-3→L + 1 (84%) |
4.89 | H→L + 2 (41%) |
181 | 5.40 | H-8→L (41%) | - | - |
5.71 | H-4→L + 2 (24%) |
Ethanol | 306 | 3.21 | H-1→L (82%) | 27,407 | 0.67 |
3.24 | H→L (82%) |
249 | 3.89 | H-3→L (86%) | - | - |
4.05 | H-1→L + 1 (84%) |
4.10 | H-4→L (64%) |
201 | 4.58 | H-2→L + 1 (89%) | - | - |
4.91 | H-1→L + 2 (33%) |
H→L + 2 (28%) |
5.07 | H-6→L (39%) |
181 | 5.41 | H→L (82%) | - | - |
5.69 | H→L (82%) |
Water | 306 | 3.21 | H-1→L (88%) | 27,437 | 0.67 |
3.25 | H→L (88%) |
249 | 3.89 | H-3→L (88%) | - | - |
4.05 | H-1→L (84%) |
4.10 | H-4→L (63%) |
201 | 4.58 | H-2→L + 1 (89%) | - | - |
4.73 | H-2→L + 2 (49%) |
4.91 | H-3→L + 1 (85%) |
181 | 5.42 | H-8→L (52%) | - | - |
5.69 | H-4→L + 2 (31%) |
Chloroform | 310 | 3.19 | H→L (83%) | | 0.60 |
249 | 3.80 | H-2→L (91%) | - | - |
3.92 | H-3→L (57%) | - | - |
4.04 | H-1→L + 1 (88%) | - | - |
4.16 | H-5→L (59%) | - | - |
204 | 4.62 | H-2→L + 1 (86%) | - | - |
4.71 | H-3→L + 1 (86%) | - | - |
4.88 | H→L + 2 (37%) | - | - |
H-7→L (26%) |
5.38 | H-6→L + 1 (28%) | - | - |
H-7→L + 1 (24%) |
Acetonitrile | 306 | 3.21 | H-1→L (86%) | 26,188 | 0.67 |
3.25 | H→L (86%) |
349 | 3.89 | H-3→L (87%) | - | - |
4.05 | H-1→L + 1 (84%) |
4.10 | H-4→L (64%) |
201 | 4.58 | H-2→L + 1 (89%) | - | - |
4.73 | H-3→L + 1 (85%) |
4.91 | H-1→L + 2 (40%) |
5.07 | H-6→L (40%) |
181 | 5.42 | H-8→L (51%) | - | - |
5.70 | H-4→L + 2 (29%) |
Acetic acid | 309 | 3.21 | H→L (64%) | 26,137 | 0.54 |
249 | 3.80 | H-2→L (93%) | - | - |
203 | 4.61 | H-2→L + 1 (87%) | - | - |
4.89 | H→L + 2 (41%) |
181 | 5.39 | H-8→L (38%) | - | - |
5.72 | H-4→L + 2 (26%) |
Table 5.
Computed intersection wavelength , nm) and optic energy gap at TD-DFT B3LYP/6-31+G(d) level as a function of several solvents.
Table 5.
Computed intersection wavelength , nm) and optic energy gap at TD-DFT B3LYP/6-31+G(d) level as a function of several solvents.
Solvent | | |
---|
THF | 350 | 3.54 |
Ethanol | 328 | 3.78 |
Water | 326 | 3.81 |
Chloroform | 354 | 3.50 |
Acetonitrile | 326 | 3.81 |
Aceticacid | 350 | 3.54 |
Table 6.
Computed excitation wavelength , nm) and fluorescence quantum yield at TD-DFT B3LYP/6-31+G(d) level as a function of several solvents.
Table 6.
Computed excitation wavelength , nm) and fluorescence quantum yield at TD-DFT B3LYP/6-31+G(d) level as a function of several solvents.
Solvent | | |
---|
THF | 320 | 0.34 |
Ethanol | 0.37 |
Water | 0.37 |
Chloroform | 0.33 |
Acetonitrile | 0.37 |
Acetic acid | 0.33 |
Table 7.
Measured maximum absorption (λabs) and emission wavelengths (λem) for 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile4 in different solvents.
Table 7.
Measured maximum absorption (λabs) and emission wavelengths (λem) for 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile4 in different solvents.
Solvents | λabs, max (nm) | λem, max (nm) | λex, max (nm) | Δf | ɸc | ɸf | Stock’s Shift |
---|
N-heptane | 300 | 346 | 300 | 0.012 | | | 46 |
CCl4 | 316 | 433 | 396 | 0.052 | 0.002 | | 117 |
Toluene | 310 | 407 | 313 | 0.099 | | 0.07 | 91 |
Hexane | 313 | 425 | 392 | 0.009 | | 0.04 | |
1,4 Dioxane | 314 | 407 | 312 | 0.164 | | 0.06 | |
THF | 313 | 344.5 | 258 | 0.207 | | | 31 |
CHCl3 | 309 | 436 | 376 | 0.259 | | | 127 |
CH2Cl2 | 312 | 409 | 311 | 0.269 | | | |
EG | 309 | 376 | 350 307 | 0.30 | | | 67 |
C4H9Cl | 311 | 431 | 310 | | | | |
DMF | 311 | 409 | 306 | 0.386 | | | |
CH3CN | 307 | 404 | 308 | 0.460 | | | |
EtOH | 307 | 372 | 306 | 0.654 | 0.003 | | 68 |
Glycerol | 310 | 411 | 365 | 0.812 | | | |
Pentanol | 307 | 410 | 307 | 0.568 | | | 102 |
H2O | 306 | 405 | 306 | 1 | | | 99 |
Dye-doped PVA | 309 | 433 | | | 0.001 | | |
SDS in aqueous solution | 307 | 406 | | | | | |
Table 8.
Zone of bacterial inhibition measured in mm of the synthesized compound 2–4.
Table 8.
Zone of bacterial inhibition measured in mm of the synthesized compound 2–4.
Microorganisms Product | Micrococcusluteus LB14110 | Listeria monocytogenes ATCC 19117 | Salmonella Typhimurium ATCC 14028 | Staphylococcus Aureus ATCC 6538 | Pseudomonas aeruginosa | Candida albicans |
---|
2 | 28 | 25 | 24 | 26 | 22 | 23 |
3 | 27 | 24 | 23 | 24 | 23 | 22 |
4 | 26 | 22 | 27 | 30 | 30 | 30 |
AMC | 25 | 22 | 20 | 23 | 20 | 22 |
Table 9.
Minimal bacterial inhibitory concentration measured in mg/mL of compounds 2–4.
Table 9.
Minimal bacterial inhibitory concentration measured in mg/mL of compounds 2–4.
Microorganism Indicator | Compound | MIC (mg/mL) |
---|
Listeria monocytogenes ATCC 19117 | 2 | 0.524 |
3 | 0.038 |
4 | 0.413 |
SalmonellaTyphimurium ATCC 14028 | 2 | 1.26 |
3 | 1.25 |
4 | 0.039 |
Micrococcus luteus LB14110 | 2 | 0.624 |
3 | 1.51 |
4 | |
Ampicillin | 0.037 |
Table 10.
Antioxidant activity of the synthesized compound was assessed by DPPH and ABTS techniques and expressed as EC50 in µg mL−1. The BHT was used as a control.
Table 10.
Antioxidant activity of the synthesized compound was assessed by DPPH and ABTS techniques and expressed as EC50 in µg mL−1. The BHT was used as a control.
EC50 in µg mL−1/ Compounds | DPPH | ABTS |
---|
2 | 48.07 | 32.21 |
3 | 47.08 | 31.23 |
4 | 49.07 | 30.22 |
BHT | 31.25 | 17.38 |
Table 11.
IC50 values of the compound for anti-inflammatory activity.
Table 11.
IC50 values of the compound for anti-inflammatory activity.
Compounds | IC50 Values in µM |
---|
Lipoxygenase Inhibition Assay | PLA2 Inhibition Assay |
---|
2 | 8.2 | 1105 |
3 | 7.3 | 1004 |
4 | 8.5 | 1110 |
Indomethacin | 8.0 | - |
Aristolochic acid | 8.1 | 25.0 |
Table 12.
IC50 of the synthesized compound (2–4) on colon carcinoma cells (HCT-116) and hepatocellular carcinoma cells lines (HepG-2).
Table 12.
IC50 of the synthesized compound (2–4) on colon carcinoma cells (HCT-116) and hepatocellular carcinoma cells lines (HepG-2).
IC50 | Compounds |
---|
HepG-2 | HCT-116 |
---|
11.75 | 7.76 | 2 |
17.45 | 13.56 | 3 |
20.65 | 15.36 | 4 |
6.05 | 3.83 | Vinblastine Standard |
Table 13.
PDB code with DOI references and full nomenclature of the studied proteins.
Table 13.
PDB code with DOI references and full nomenclature of the studied proteins.
Protein | PDB ID | PDB DOI | Full Name |
---|
Lipoxygenase | 6N2W | 10.2210/pdb6 NRW/pdb | Crystal structure of Dpr1 IG1 bound to DIP-eta IG1 |
4NRE | 10.2210/pdb4NRE/pdb | The structure of human 15-lipoxygenase-2 with a substrate mimic |
PLA2 | 1TH6 | 10.2210/pdb1TH6/pdb | Crystal structure of phospholipase A2 in complex with atropine at 1.23 A resolution |
2QU9 | 10.2210/pdb2QU9/pdb | Crystal structure of the complex of group II phospholipase A2 with eugenol |
4DBK | 10.2210/pdb4DBK/pdb | Crystal structure of porcine pancreatic phospholipase A2 complexed with berberine |
HepG-2 | 2W3L | 10.2210/pdb2W3L/pdb | Crystal structure of Chimeric Bcl2-xL and Phenyl Tetrahydroisoquinoline Amide Complex |
HCT-116 | 1YWN | 10.2210/pdb1YWN/pdb | Vegfr2 in complex with a novel 4-amino-furo[2,3-d]pyrimidine |
Table 14.
Resolution of the crystal structures of the studied proteins in (Å), computed number of detected cavities, best protein cavity volume in () and the predicted binding free energy of the interaction between the inhibitor and the protein () in (kcal·mol−1).
Table 14.
Resolution of the crystal structures of the studied proteins in (Å), computed number of detected cavities, best protein cavity volume in () and the predicted binding free energy of the interaction between the inhibitor and the protein () in (kcal·mol−1).
Anti-Inflammatory Activity |
---|
Protein | Resolution | n | Volume | Eb |
---|
6N2W (Lipoxygenase) | 2.40 | 34 | 1155 | −10.3 |
4NRE (Lipoxygenase) | 2.63 | 33 | 2171 | −8.3 |
1TH6 (PLA2) | 1.23 | 6 | 1247 | −9.0 |
2QU9 (PLA2) | 2.08 | 5 | 670 | −8.9 |
4DBK (PLA2) | 2.30 | 9 | 650 | −8.8 |
Antiproliferative activity |
2W3L (HepG-2) | 2.10 | 7 | 534 | −8.8 |
1YWN (HCT-116) | 1.71 | 18 | 1096 | −8.7 |
Table 15.
Figures a and b: (a) best position of the coumarin4 inhibitor within the studied proteins; (b) 2D diagram of the interactions that occurred between the 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4 inhibitor and the amino acids of the proteins.