Some 6,8-dichloro-quinolone compounds were designed and synthesized; by comparing with 6-fluoro-8... more Some 6,8-dichloro-quinolone compounds were designed and synthesized; by comparing with 6-fluoro-8-chloro-quinolone compounds, the influence of the nature of the halogen atom from six position of the quinolone ring on the molecular properties and on the antimicrobial activity was studied. The DFT/B3LYP/6-311G* level of basis set was used for the computation of molecular structure of optimized compounds. The calculations of characteristics and molecular properties were performed using Spartan'14 Software from Wavefunction, Inc. Irvine, CA. The HOMO-LUMO energies and orbitals, global reactivity descriptors, various thermodynamic parameters, and dipole moment (μ) were calculated to determine the molecular properties of quinolone compounds. Molecular docking studies were realized to identify and visualize the most likely interaction ligand (quinolone/fluoroquinolone compounds) with the protein receptor. The score and hydrogen bonds formed with the amino acids from group interaction atoms are used to predict the binding modes, the binding affinities, and the orientation of the docked quinolone/fluoroquinolone derivatives in the active site of the protein receptor. The protein-ligand complex was realized based on the X-ray structure of Bacillus cereus (PDB ID: 1VEN) using CLC Drug Discovery Workbench 2.4 software. The quinolone compounds were characterized by physical-chemical methods (elemental analysis, IR spectral analysis, 1H-NMR, 13C-NMR spectra, UV-Vis, thin layer chromatography) and by antimicrobial activity against some Gram-positive and Gramnegative microorganisms: Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Micrococcus luteus, Escherichia coli and Pseudomonas aeruginosa.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Prostaglandins (PGs) with cytoprotective activity were studied for a long time, and a few PGE1 an... more Prostaglandins (PGs) with cytoprotective activity were studied for a long time, and a few PGE1 and PGE2 stable analogues were promoted as drugs: arbaprostil, enprostil, misoprostol, and rioptostol. Similarly, nocloprost, a 9β-chlorine prostaglandin analogue, and many 9β-and 11βsubstituted prostaglandins were synthesized and studied for their biological activity. We previously synthesized new 9β-halogenated prostaglandins with an ester group at the carbon atom 6 (PGs numbering) by the reaction of a δ-lactone intermediate with diols in acid catalysis. These compounds were used in the current molecular docking study to determine their potential cytoprotective (anti-ulcer) activity. The current study was done with the CLC Drug Discovery Workbench 2.4. software and an oxidoreductase enzyme receptor, chosen from the Protein Data Bank, ID: 4KEW (www.rcsb.org). We used two recognized drugs, omeprazole (co-crystallized with the enzyme) and nocloprost, as the standard. The 9β-halogenated prostaglandin analogs were docked. Nocloprost and all 9β-halogenated compounds had docking scores greater than that of omeprazole. The majority of the 9β-halogenated analogs had docking scores even greater than that of nocloprost, indicating that these compounds could have potential cytoprotective (anti-ulcer) activity. A few correlations between docking score and substituents on the prostaglandin skeleton were found.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Ten natural and semi-synthetic compounds (gallic acid and alkyl gallates) were investigated by in... more Ten natural and semi-synthetic compounds (gallic acid and alkyl gallates) were investigated by in silico methods in order to evaluate their potential inhibitory activity against SAR-CoV-2 using the X-ray structure of SARS-CoV-2 main protease bound to Boceprevir at 1.45 Å (PDB ID: 6WNP). The evaluation of drug-likeness in terms of Lipinski's Rule of Five and docking results in terms of docking score and interactions with the amino acids residues from the active binding site of the target protein were reported.
Stokesia laevis (common name Stokes aster) ethanolic extract (Slae26) containing 5 mg GAE/mL extr... more Stokesia laevis (common name Stokes aster) ethanolic extract (Slae26) containing 5 mg GAE/mL extract was investigated to establish cytotoxicity and anti-proliferative effects. The assays were performed on normal murine fibroblast cell line L929 and malignant murine melanoma cell line B16, respectively; for the first time in literature data, potential cytotoxic and anti-proliferative effects of the ethanolic extract from S. laevis on both, normal murine fibroblast cell line L929, and murine melanoma cell line B16 have been proved. The study is supplemented by molecular docking simulations of the major components of Slae26 against human tyrosinase receptor, to evaluate possible melanogenesis inhibition.
ized, where HL is the binucleating ligand 2,6-diformyl-4-methylphenoldi(benzoylhydrazone). Based ... more ized, where HL is the binucleating ligand 2,6-diformyl-4-methylphenoldi(benzoylhydrazone). Based on the IR spectra, elemental analyses, conductivity measurements and thermal analysis, these complexes are proposed to have an endogenous phenoxide bridge and an exogenous chloride bridge. The ligand field parameters of the nickel(I1) complex were obtained from near-IR spectra. The variable magnetic susceptibility (4-300 K) data of the manganese(II), iron(cobalt(II) and nickel(I1) complexes indicated that the magnetic interactions between metal ions were very weak.
The main goal of this chapter is to reveal the importance of molecular structure analysis with sp... more The main goal of this chapter is to reveal the importance of molecular structure analysis with specific computational tools using quantum chemistry methods based on density functional theory (DFT) with focus on pharmaceutical compounds. A wide series of molecular properties and descriptors related with chemical reactivity is discussed and compared for small organic molecules (e.g., quinolones, oxazolidinones). Structural and physicochemical information, important for quantitative structure-property relationships (QSPR) and quantitative structure-activity relationships (QSAR) modeling analysis, obtained using Spartan 14 software Wavefunction, are reported. Thus, by a computational procedure including energy minimization and predictive calculations, values of quantum chemical parameters and molecular properties related with electronic charge distribution are reported and discussed. Frontier molecular orbitals energy diagram and their bandgap provide indications about chemical reactivity and kinetic stability of the molecules. Derived parameters (ionization potential (I), electron affinity (A), electronegativity (χ), global hardness (η), softness (σ), chemical potential (μ) and global electrophilicity index (ω)) are given. Also, graphic quantities are reported: electrostatic potential maps, local ionization potential maps and LUMO maps, as visual representation of the chemically active sites and comparative reactivity of different constitutive atoms.
egyptian journal of basic and applied sciences, 2021
The novel Coronavirus Disease 2019 (COVID-19) has emerged as a global pandemic and has posed seri... more The novel Coronavirus Disease 2019 (COVID-19) has emerged as a global pandemic and has posed serious health hazards for the humanity since December 2019. Over 2.5 million deaths have been reported worldwide till date mainly due to rapid human-to-human transmission of this virus while affecting millions of people. The widespread propagation of this disease has radically changed the common practice of human's normal life. Numerous measures have been taken up by different health agencies and government bodies of several countries to combat the menace by attenuating the transmission of SARS-CoV-2. The emergence of a new UK variant B.1.1.7 of the virus in some countries has indeed aggravated the issue of tackling the disease. The virus mainly transmits through coughs, sneezes, talks, or breathes. The airborne transmission is also an alternate dominant route. This opinion focuses on the infection capability of SARS-CoV-2 on different surfaces and also other possible means of transmission.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Coronavirus disease (COVID-19) is an infectious disease caused by coronavirus 2 (SARS-CoV-2) whic... more Coronavirus disease (COVID-19) is an infectious disease caused by coronavirus 2 (SARS-CoV-2) which was detected for the first time in Wuhan China in December 2019. The rapid spread of this highly contagious and pathogenic virus led to the declaration of the pandemic by the World Health Organization (WHO) on March 11, 2020. In these conditions, the discovery of new antiviral agents is extremely important. For the development of the anti-SARS-CoV-2 drugs, the fastest way is to find potential molecules from the marketed drugs by molecular docking studies.
Oxymercuration of (±)-(1α,3α,3aβ,6aβ)-1,2,3,3a,4,6a-hexahydro-1,3-pentalenedimethanol dibenzoate ... more Oxymercuration of (±)-(1α,3α,3aβ,6aβ)-1,2,3,3a,4,6a-hexahydro-1,3-pentalenedimethanol dibenzoate 1 was performed with mercuric tetrafluoroborate alone, in the presence of tetrafluoroboric acid and with tetrafluoroboric acid + sodium acetate and demercuration with sodium borohydride in 3N NaOH. The hydration of the alkene was selective toward the symmetric alcohol at short time, but at prolonged time, the symmetric and un-symmetric alcohols were obtained in a near 1:1 ratio. Anyway, the oxymercurationdemercuration of alkene 1 is a slow hydration reaction.
Prostaglandins with cytoprotective activity were studied for a long time and a few PGE1 and PGE2 ... more Prostaglandins with cytoprotective activity were studied for a long time and a few PGE1 and PGE2 stable analogs were promoted as drugs: arbaprostil, enprostil, misoprostol and rioptostol. Nocloprost, a 9β-chlorine prostaglandin analog, has been also promoted as a cytoprotective drug; the succes with this compound stimulated the reserches, and many 9β-or 11β-substituted prostaglandins were synthesized and studied for their biological activity. In the same dirrection we previously synthesized new 9β-halogenated prostaglandins having also an ester group at the carbon atom 6. These compounds were now used in a molecular docking study to predict their potential cytoprotective (anti-ulcer) activity. The study has been done with CLC Drug Discovery Workbench 2.4. software and an oxidoreductase enzyme receptor, chosen from the Protein Data Bank, ID: 4KEW. Two recognized drugs, omeprazole (co-crystallized with the enzyme) and nocloprost were used as standard in the study. The 9β-halogenated prostaglandin analogs were finally docked. Nocloprost and all 9βhalogenated compounds had docking score greater than that of omeprazole. The majority of the 9βhalogenated analogs have a docking score even greater than that of nocloprost, indicating that these compounds could have potential cytoprotective activity. Correlations between docking score and substituents on the prostaglandin skeleton have been done.
International Journal of Molecular Sciences, Feb 4, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
A new series of fluoroquinolone compounds have been obtained by Gould-Jacobs method. The compound... more A new series of fluoroquinolone compounds have been obtained by Gould-Jacobs method. The compounds have been characterized by physic-chemical methods (elemental analysis, FTIR, NMR, UV-Vis) and by antimicrobial activity against Gram-positive and Gram-negative microorganisms. For the synthesized compounds have been performed calculations of characteristics and molecular properties, using Spartan'14 Software from Wavefunction, Inc. Irvine, CA. and molecular docking studies using CLC Drug Discovery Workbench 2.4 software, to identify and visualize the most likely interaction ligand (fluoroquinolone) with the receptor protein.
Some 6,8-dichloro-quinolone compounds were designed and synthesized; by comparing with 6-fluoro-8... more Some 6,8-dichloro-quinolone compounds were designed and synthesized; by comparing with 6-fluoro-8-chloro-quinolone compounds, the influence of the nature of the halogen atom from six position of the quinolone ring on the molecular properties and on the antimicrobial activity was studied. The DFT/B3LYP/6-311G* level of basis set was used for the computation of molecular structure of optimized compounds. The calculations of characteristics and molecular properties were performed using Spartan'14 Software from Wavefunction, Inc. Irvine, CA. The HOMO-LUMO energies and orbitals, global reactivity descriptors, various thermodynamic parameters, and dipole moment (μ) were calculated to determine the molecular properties of quinolone compounds. Molecular docking studies were realized to identify and visualize the most likely interaction ligand (quinolone/fluoroquinolone compounds) with the protein receptor. The score and hydrogen bonds formed with the amino acids from group interaction atoms are used to predict the binding modes, the binding affinities, and the orientation of the docked quinolone/fluoroquinolone derivatives in the active site of the protein receptor. The protein-ligand complex was realized based on the X-ray structure of Bacillus cereus (PDB ID: 1VEN) using CLC Drug Discovery Workbench 2.4 software. The quinolone compounds were characterized by physical-chemical methods (elemental analysis, IR spectral analysis, 1H-NMR, 13C-NMR spectra, UV-Vis, thin layer chromatography) and by antimicrobial activity against some Gram-positive and Gramnegative microorganisms: Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Micrococcus luteus, Escherichia coli and Pseudomonas aeruginosa.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Prostaglandins (PGs) with cytoprotective activity were studied for a long time, and a few PGE1 an... more Prostaglandins (PGs) with cytoprotective activity were studied for a long time, and a few PGE1 and PGE2 stable analogues were promoted as drugs: arbaprostil, enprostil, misoprostol, and rioptostol. Similarly, nocloprost, a 9β-chlorine prostaglandin analogue, and many 9β-and 11βsubstituted prostaglandins were synthesized and studied for their biological activity. We previously synthesized new 9β-halogenated prostaglandins with an ester group at the carbon atom 6 (PGs numbering) by the reaction of a δ-lactone intermediate with diols in acid catalysis. These compounds were used in the current molecular docking study to determine their potential cytoprotective (anti-ulcer) activity. The current study was done with the CLC Drug Discovery Workbench 2.4. software and an oxidoreductase enzyme receptor, chosen from the Protein Data Bank, ID: 4KEW (www.rcsb.org). We used two recognized drugs, omeprazole (co-crystallized with the enzyme) and nocloprost, as the standard. The 9β-halogenated prostaglandin analogs were docked. Nocloprost and all 9β-halogenated compounds had docking scores greater than that of omeprazole. The majority of the 9β-halogenated analogs had docking scores even greater than that of nocloprost, indicating that these compounds could have potential cytoprotective (anti-ulcer) activity. A few correlations between docking score and substituents on the prostaglandin skeleton were found.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Ten natural and semi-synthetic compounds (gallic acid and alkyl gallates) were investigated by in... more Ten natural and semi-synthetic compounds (gallic acid and alkyl gallates) were investigated by in silico methods in order to evaluate their potential inhibitory activity against SAR-CoV-2 using the X-ray structure of SARS-CoV-2 main protease bound to Boceprevir at 1.45 Å (PDB ID: 6WNP). The evaluation of drug-likeness in terms of Lipinski's Rule of Five and docking results in terms of docking score and interactions with the amino acids residues from the active binding site of the target protein were reported.
Stokesia laevis (common name Stokes aster) ethanolic extract (Slae26) containing 5 mg GAE/mL extr... more Stokesia laevis (common name Stokes aster) ethanolic extract (Slae26) containing 5 mg GAE/mL extract was investigated to establish cytotoxicity and anti-proliferative effects. The assays were performed on normal murine fibroblast cell line L929 and malignant murine melanoma cell line B16, respectively; for the first time in literature data, potential cytotoxic and anti-proliferative effects of the ethanolic extract from S. laevis on both, normal murine fibroblast cell line L929, and murine melanoma cell line B16 have been proved. The study is supplemented by molecular docking simulations of the major components of Slae26 against human tyrosinase receptor, to evaluate possible melanogenesis inhibition.
ized, where HL is the binucleating ligand 2,6-diformyl-4-methylphenoldi(benzoylhydrazone). Based ... more ized, where HL is the binucleating ligand 2,6-diformyl-4-methylphenoldi(benzoylhydrazone). Based on the IR spectra, elemental analyses, conductivity measurements and thermal analysis, these complexes are proposed to have an endogenous phenoxide bridge and an exogenous chloride bridge. The ligand field parameters of the nickel(I1) complex were obtained from near-IR spectra. The variable magnetic susceptibility (4-300 K) data of the manganese(II), iron(cobalt(II) and nickel(I1) complexes indicated that the magnetic interactions between metal ions were very weak.
The main goal of this chapter is to reveal the importance of molecular structure analysis with sp... more The main goal of this chapter is to reveal the importance of molecular structure analysis with specific computational tools using quantum chemistry methods based on density functional theory (DFT) with focus on pharmaceutical compounds. A wide series of molecular properties and descriptors related with chemical reactivity is discussed and compared for small organic molecules (e.g., quinolones, oxazolidinones). Structural and physicochemical information, important for quantitative structure-property relationships (QSPR) and quantitative structure-activity relationships (QSAR) modeling analysis, obtained using Spartan 14 software Wavefunction, are reported. Thus, by a computational procedure including energy minimization and predictive calculations, values of quantum chemical parameters and molecular properties related with electronic charge distribution are reported and discussed. Frontier molecular orbitals energy diagram and their bandgap provide indications about chemical reactivity and kinetic stability of the molecules. Derived parameters (ionization potential (I), electron affinity (A), electronegativity (χ), global hardness (η), softness (σ), chemical potential (μ) and global electrophilicity index (ω)) are given. Also, graphic quantities are reported: electrostatic potential maps, local ionization potential maps and LUMO maps, as visual representation of the chemically active sites and comparative reactivity of different constitutive atoms.
egyptian journal of basic and applied sciences, 2021
The novel Coronavirus Disease 2019 (COVID-19) has emerged as a global pandemic and has posed seri... more The novel Coronavirus Disease 2019 (COVID-19) has emerged as a global pandemic and has posed serious health hazards for the humanity since December 2019. Over 2.5 million deaths have been reported worldwide till date mainly due to rapid human-to-human transmission of this virus while affecting millions of people. The widespread propagation of this disease has radically changed the common practice of human's normal life. Numerous measures have been taken up by different health agencies and government bodies of several countries to combat the menace by attenuating the transmission of SARS-CoV-2. The emergence of a new UK variant B.1.1.7 of the virus in some countries has indeed aggravated the issue of tackling the disease. The virus mainly transmits through coughs, sneezes, talks, or breathes. The airborne transmission is also an alternate dominant route. This opinion focuses on the infection capability of SARS-CoV-2 on different surfaces and also other possible means of transmission.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Coronavirus disease (COVID-19) is an infectious disease caused by coronavirus 2 (SARS-CoV-2) whic... more Coronavirus disease (COVID-19) is an infectious disease caused by coronavirus 2 (SARS-CoV-2) which was detected for the first time in Wuhan China in December 2019. The rapid spread of this highly contagious and pathogenic virus led to the declaration of the pandemic by the World Health Organization (WHO) on March 11, 2020. In these conditions, the discovery of new antiviral agents is extremely important. For the development of the anti-SARS-CoV-2 drugs, the fastest way is to find potential molecules from the marketed drugs by molecular docking studies.
Oxymercuration of (±)-(1α,3α,3aβ,6aβ)-1,2,3,3a,4,6a-hexahydro-1,3-pentalenedimethanol dibenzoate ... more Oxymercuration of (±)-(1α,3α,3aβ,6aβ)-1,2,3,3a,4,6a-hexahydro-1,3-pentalenedimethanol dibenzoate 1 was performed with mercuric tetrafluoroborate alone, in the presence of tetrafluoroboric acid and with tetrafluoroboric acid + sodium acetate and demercuration with sodium borohydride in 3N NaOH. The hydration of the alkene was selective toward the symmetric alcohol at short time, but at prolonged time, the symmetric and un-symmetric alcohols were obtained in a near 1:1 ratio. Anyway, the oxymercurationdemercuration of alkene 1 is a slow hydration reaction.
Prostaglandins with cytoprotective activity were studied for a long time and a few PGE1 and PGE2 ... more Prostaglandins with cytoprotective activity were studied for a long time and a few PGE1 and PGE2 stable analogs were promoted as drugs: arbaprostil, enprostil, misoprostol and rioptostol. Nocloprost, a 9β-chlorine prostaglandin analog, has been also promoted as a cytoprotective drug; the succes with this compound stimulated the reserches, and many 9β-or 11β-substituted prostaglandins were synthesized and studied for their biological activity. In the same dirrection we previously synthesized new 9β-halogenated prostaglandins having also an ester group at the carbon atom 6. These compounds were now used in a molecular docking study to predict their potential cytoprotective (anti-ulcer) activity. The study has been done with CLC Drug Discovery Workbench 2.4. software and an oxidoreductase enzyme receptor, chosen from the Protein Data Bank, ID: 4KEW. Two recognized drugs, omeprazole (co-crystallized with the enzyme) and nocloprost were used as standard in the study. The 9β-halogenated prostaglandin analogs were finally docked. Nocloprost and all 9βhalogenated compounds had docking score greater than that of omeprazole. The majority of the 9βhalogenated analogs have a docking score even greater than that of nocloprost, indicating that these compounds could have potential cytoprotective activity. Correlations between docking score and substituents on the prostaglandin skeleton have been done.
International Journal of Molecular Sciences, Feb 4, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
A new series of fluoroquinolone compounds have been obtained by Gould-Jacobs method. The compound... more A new series of fluoroquinolone compounds have been obtained by Gould-Jacobs method. The compounds have been characterized by physic-chemical methods (elemental analysis, FTIR, NMR, UV-Vis) and by antimicrobial activity against Gram-positive and Gram-negative microorganisms. For the synthesized compounds have been performed calculations of characteristics and molecular properties, using Spartan'14 Software from Wavefunction, Inc. Irvine, CA. and molecular docking studies using CLC Drug Discovery Workbench 2.4 software, to identify and visualize the most likely interaction ligand (fluoroquinolone) with the receptor protein.
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