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Structural and spectral investigations of the recently synthesized chalcone (E)-3-mesityl-1-(naphthalen-2-yl) prop-2-en-1-one, a potential chemotherapeutic agent.

Barakat A, Al-Majid AM, Soliman SM, Mabkhot YN, Ali M, Ghabbour HA, Fun HK, Wadood A - Chem Cent J (2015)

Bottom Line: The calculated IR fundamental bands were assigned and compared with the experimental data.Molecular stability was successfully analyzed using NBO and electron delocalization is confirmed by MEP.Graphical Abstract(E)-3-Mesityl-1-(naphthalen-2-yl) prop-2-en-1-one: a crystal structure and computational studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, 11451 Riyadh, Saudi Arabia ; Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, 21321 Alexandria, Ibrahimia Egypt.

ABSTRACT

Background: Chalcones (1,3-diaryl-2-propen-1-ones, represent an important subgroup of the polyphenolic family, which have shown a wide spectrum of medical and industrial application. Due to their redundancy in plants and ease of preparation, this category of molecules has inspired considerable attention for potential therapeutic uses. They are also effective in vivo as anti-tumor promoting, cell proliferating inhibitors and chemo preventing agents.

Results: Synthesis and molecular structure investigation of (E)-3-mesityl-1-(naphthalen-2-yl) prop-2-en-1-one (3) is reported. The structure of the title compound 3 is confirmed by X-ray crystallography. The optimized molecular structure of the studied compound is calculated using DFT B3LYP/6-311G (d,p) method. The calculated geometric parameters are in good agreement with the experimental data obtained from our reported X-ay structure. The calculated IR fundamental bands were assigned and compared with the experimental data. The electronic spectra of the studied compound have been calculated using the time dependant density functional theory (TD-DFT). The longest wavelength band is due to H → L (79 %) electronic transition which belongs to π-π* excitation. The (1)H- and (13)C-NMR chemical shifts were calculated using gauge independent atomic orbitals (GIAO) method, which showed good correlations with the experimental data (R(2) = 0.9911-0.9965). The natural bond orbital (NBO) calculations were performed to predict the natural atomic charges at different atomic sites. The molecular electrostatic potential (MEP) was used to visualize the charge distribution on the molecule. Molecular docking results suggest that the compound might exhibit inhibitory activity against GPb and may act as potential anti-diabetic compound.

Conclusions: (E)-3-Mesityl-1-(naphthalen-2-yl) prop-2-en-1-one single crystal is grown and characterized by single crystal X-ray diffraction, FT-IR, UV-vis, DFT and optimized geometrical parameters are close to the experimental bond lengths and angles. Molecular stability was successfully analyzed using NBO and electron delocalization is confirmed by MEP. Prediction of Activity Spectra Analysis of the title compound, predicts anti-diabetic activity with probability to have an active value of 0.348. Graphical Abstract(E)-3-Mesityl-1-(naphthalen-2-yl) prop-2-en-1-one: a crystal structure and computational studies.

No MeSH data available.


Related in: MedlinePlus

a The title compound 3 was fit well in the cavity of histone acetyltransferase enzyme. b Docking conformation of title compound 3 (generated by MOE docking software) properly accommodated into the binding cavity of histone acetyltransferase enzyme and developed hydrogen bond and two arene-cation and arene-arene interactions with active site residue Arg176, Arg124 and Trp180. histone acetyltransferase
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Fig12: a The title compound 3 was fit well in the cavity of histone acetyltransferase enzyme. b Docking conformation of title compound 3 (generated by MOE docking software) properly accommodated into the binding cavity of histone acetyltransferase enzyme and developed hydrogen bond and two arene-cation and arene-arene interactions with active site residue Arg176, Arg124 and Trp180. histone acetyltransferase

Mentions: PASS (Prediction of Activity Spectra) is an online tool [46] which predicts almost 900 types of activities based on the structure of a compound. PASS analysis (Additional file 1: Table S5) of the title compound 3 predicts anti-diabetic activity (human histone acetyltransferase) with Pa (probability to be active) value of 0.348. To evaluate the inhibitory nature of the title compound against human histone acetyltransferase, molecular docking simulations were carried out. Molecular docking is an efficient method to get an insight into ligand-receptor interactions. Molecular docking studies were performed using Molecular Operating Environment (MOE) software (www.chemcomp.com). The 3D crystal structure of human histone acetyltransferase was downloaded from Protein Data Bank (PDB ID: 4PZS) [47]. Before docking experiment, the title compound 3 was prepared for docking by minimizing its energy at B3LYP functional and 6–311G (d,p) basis set using Gaussian 03 software. Partial charges were calculated by Gasteiger method. Most macromolecular crystal structures contain little or no hydrogen coordinate data due to limited resolution and thus protonation was done prior to docking using Protonate 3D tools implemented in MOE. Protonation was followed by energy minimization up to 0.05 Gradient using Amber99 force field. The docking protocol predicted the same conformation as was present in the crystal structure with RMSD value close to the allowed range [48] and surrounded by the same active site residues of the enzyme. Amongst the generated docking conformations the top-ranked conformation was visualized for ligand-enzyme interaction using PyMol. Analysis of the docking results showed that the synthesized compound 3 fit well within the active site of histone acetyltransferase enzyme (Fig. 12a). From the docking conformation it was observed that both the naphthalene, mesitylene moiety as well as the carbonyl oxygen of 2-methylprop-1-ene moiety of the compound 3 interact with important active site residues of the enzyme, e.g., Arg124, Arg176 and Trp180. Arg176 was found in making two arene-cation interactions with both the phenyl ring of naphthalene moiety, Arg124 was involved in interaction with carbonyl oxygen of 2-methylprop-1-ene moiety and Trp180 was found in sharing its π-electron with the phenyl ring of the compound 3 and making π- π interaction by which they stabilized the structure (Fig. 12b). The presence of one H-bond, one arene-arene and two arene-cation interactions confirm that the inhibitor may be specific to this site. These preliminary results suggest that the compound 3 might exhibit inhibitory activity against histone acetyltransferase enzyme and may act as potential anti-cancer compound. However, further biological tests should be done to validate the computational predictions.Fig. 12


Structural and spectral investigations of the recently synthesized chalcone (E)-3-mesityl-1-(naphthalen-2-yl) prop-2-en-1-one, a potential chemotherapeutic agent.

Barakat A, Al-Majid AM, Soliman SM, Mabkhot YN, Ali M, Ghabbour HA, Fun HK, Wadood A - Chem Cent J (2015)

a The title compound 3 was fit well in the cavity of histone acetyltransferase enzyme. b Docking conformation of title compound 3 (generated by MOE docking software) properly accommodated into the binding cavity of histone acetyltransferase enzyme and developed hydrogen bond and two arene-cation and arene-arene interactions with active site residue Arg176, Arg124 and Trp180. histone acetyltransferase
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4477317&req=5

Fig12: a The title compound 3 was fit well in the cavity of histone acetyltransferase enzyme. b Docking conformation of title compound 3 (generated by MOE docking software) properly accommodated into the binding cavity of histone acetyltransferase enzyme and developed hydrogen bond and two arene-cation and arene-arene interactions with active site residue Arg176, Arg124 and Trp180. histone acetyltransferase
Mentions: PASS (Prediction of Activity Spectra) is an online tool [46] which predicts almost 900 types of activities based on the structure of a compound. PASS analysis (Additional file 1: Table S5) of the title compound 3 predicts anti-diabetic activity (human histone acetyltransferase) with Pa (probability to be active) value of 0.348. To evaluate the inhibitory nature of the title compound against human histone acetyltransferase, molecular docking simulations were carried out. Molecular docking is an efficient method to get an insight into ligand-receptor interactions. Molecular docking studies were performed using Molecular Operating Environment (MOE) software (www.chemcomp.com). The 3D crystal structure of human histone acetyltransferase was downloaded from Protein Data Bank (PDB ID: 4PZS) [47]. Before docking experiment, the title compound 3 was prepared for docking by minimizing its energy at B3LYP functional and 6–311G (d,p) basis set using Gaussian 03 software. Partial charges were calculated by Gasteiger method. Most macromolecular crystal structures contain little or no hydrogen coordinate data due to limited resolution and thus protonation was done prior to docking using Protonate 3D tools implemented in MOE. Protonation was followed by energy minimization up to 0.05 Gradient using Amber99 force field. The docking protocol predicted the same conformation as was present in the crystal structure with RMSD value close to the allowed range [48] and surrounded by the same active site residues of the enzyme. Amongst the generated docking conformations the top-ranked conformation was visualized for ligand-enzyme interaction using PyMol. Analysis of the docking results showed that the synthesized compound 3 fit well within the active site of histone acetyltransferase enzyme (Fig. 12a). From the docking conformation it was observed that both the naphthalene, mesitylene moiety as well as the carbonyl oxygen of 2-methylprop-1-ene moiety of the compound 3 interact with important active site residues of the enzyme, e.g., Arg124, Arg176 and Trp180. Arg176 was found in making two arene-cation interactions with both the phenyl ring of naphthalene moiety, Arg124 was involved in interaction with carbonyl oxygen of 2-methylprop-1-ene moiety and Trp180 was found in sharing its π-electron with the phenyl ring of the compound 3 and making π- π interaction by which they stabilized the structure (Fig. 12b). The presence of one H-bond, one arene-arene and two arene-cation interactions confirm that the inhibitor may be specific to this site. These preliminary results suggest that the compound 3 might exhibit inhibitory activity against histone acetyltransferase enzyme and may act as potential anti-cancer compound. However, further biological tests should be done to validate the computational predictions.Fig. 12

Bottom Line: The calculated IR fundamental bands were assigned and compared with the experimental data.Molecular stability was successfully analyzed using NBO and electron delocalization is confirmed by MEP.Graphical Abstract(E)-3-Mesityl-1-(naphthalen-2-yl) prop-2-en-1-one: a crystal structure and computational studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, 11451 Riyadh, Saudi Arabia ; Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, 21321 Alexandria, Ibrahimia Egypt.

ABSTRACT

Background: Chalcones (1,3-diaryl-2-propen-1-ones, represent an important subgroup of the polyphenolic family, which have shown a wide spectrum of medical and industrial application. Due to their redundancy in plants and ease of preparation, this category of molecules has inspired considerable attention for potential therapeutic uses. They are also effective in vivo as anti-tumor promoting, cell proliferating inhibitors and chemo preventing agents.

Results: Synthesis and molecular structure investigation of (E)-3-mesityl-1-(naphthalen-2-yl) prop-2-en-1-one (3) is reported. The structure of the title compound 3 is confirmed by X-ray crystallography. The optimized molecular structure of the studied compound is calculated using DFT B3LYP/6-311G (d,p) method. The calculated geometric parameters are in good agreement with the experimental data obtained from our reported X-ay structure. The calculated IR fundamental bands were assigned and compared with the experimental data. The electronic spectra of the studied compound have been calculated using the time dependant density functional theory (TD-DFT). The longest wavelength band is due to H → L (79 %) electronic transition which belongs to π-π* excitation. The (1)H- and (13)C-NMR chemical shifts were calculated using gauge independent atomic orbitals (GIAO) method, which showed good correlations with the experimental data (R(2) = 0.9911-0.9965). The natural bond orbital (NBO) calculations were performed to predict the natural atomic charges at different atomic sites. The molecular electrostatic potential (MEP) was used to visualize the charge distribution on the molecule. Molecular docking results suggest that the compound might exhibit inhibitory activity against GPb and may act as potential anti-diabetic compound.

Conclusions: (E)-3-Mesityl-1-(naphthalen-2-yl) prop-2-en-1-one single crystal is grown and characterized by single crystal X-ray diffraction, FT-IR, UV-vis, DFT and optimized geometrical parameters are close to the experimental bond lengths and angles. Molecular stability was successfully analyzed using NBO and electron delocalization is confirmed by MEP. Prediction of Activity Spectra Analysis of the title compound, predicts anti-diabetic activity with probability to have an active value of 0.348. Graphical Abstract(E)-3-Mesityl-1-(naphthalen-2-yl) prop-2-en-1-one: a crystal structure and computational studies.

No MeSH data available.


Related in: MedlinePlus