Bahaa El-Dien El-Gendy | Benha University (original) (raw)
Papers by Bahaa El-Dien El-Gendy
RSC Advances
4-Isopropyl–thiotropolone was identified as a novel anti-microbial agent with good therapeutic in... more 4-Isopropyl–thiotropolone was identified as a novel anti-microbial agent with good therapeutic index and ADME properties.
Protection of Metals and Physical Chemistry of Surfaces
Three novel inhibitors based on 4,5,6,7-tetrahydrobenzo[b]thiophene scaffold were synthesized and... more Three novel inhibitors based on 4,5,6,7-tetrahydrobenzo[b]thiophene scaffold were synthesized and characterized. The inhibitive action of the synthesized inhibitors toward carbon steel acid corrosion was investigated using weight loss and polarization techniques. It was found that the three compounds act as good corrosion inhibitor for carbon steel in the acidic medium. The inhibition efficiency was found to increase with increasing concentration and decreased with increasing temperature. The adsorption of inhibitors molecules on the carbon steel surface follows Langmuir adsorption isotherm. The correlation between the inhibitors structures and their corrosion inhibition action was studied by quantum chemical calculations.
Current Pharmaceutical Design
BACKGROUND Hepatitis C virus (HCV) infection poses a considerable threat to the public health. Th... more BACKGROUND Hepatitis C virus (HCV) infection poses a considerable threat to the public health. The current standard of care treatment with pegylated interferon-alpha in combination with ribavirin (PEG-IFN- α+RBV) is associated with significant side effects, poorly tolerated, and provides limited efficacy. The development of direct-acting antiviral agents (DAAs) targeting key viral enzymes essential for viral replication represents a significant milestone in the treatment of chronic HCV infection. Given its critical role in the viral polyprotein processing and the evasion of the host innate immunity, the NS3/4A protease has emerged as a promising drug target for the development of anti-HCV therapies. Although several potent NS3/4A protease inhibitors (PIs) have been approved or are in clinical development, the majority of currently available PIs have significant limitations related to untoward adverse events and a lack of pan-genotypic activity, indicating a continuing unmet medical need for the development and optimization of novel PIs with improved efficacy and tolerability, convenient dosing schedules, and shorter treatment durations. METHODS The inhibitory efficacy of four computer-designed chemically-synthesized compounds was evaluated against in vitro-expressed NS3/4A protease from HCV genotype 4a, the most prevalent genotype in Egypt, using a fluorescence-based enzymatic assay. RESULTS We successfully identified two non-macrocyclic small molecules, BE113 (7a) and BE114 (7b), which exhibited inhibitory activity against HCV NS3/4A protease from HCV genotype 4a. CONCLUSION The two compounds presented in this study may be promising inhibitors against NS3/4A protease of HCV genotype 4a and could be novel lead compounds for developing new therapeutics for the treatment of chronic HCV infection.
Journal of Medicinal Chemistry
Nuclear hormone receptors represent a large family of ligand-activated transcription factors that... more Nuclear hormone receptors represent a large family of ligand-activated transcription factors that include steroid receptors, thyroid/retinoid receptors, and orphan receptors. Among nuclear hormone receptors, the liver X receptors have emerged as very important drug targets. These receptors regulate some of the most important metabolic functions, and they were also identified as anti-inflammatory transcription factors and regulators of the immune system. The development of drugs targeting liver X receptors continues to be a challenge, but advances in our knowledge of receptor structure and function move us forward, toward achieving this goal. This review highlights the latest advances in the development of synthetic LXR modulators in the primary literature from 2013 to 2017. In this review, we place great emphasis on the structure and function of LXRs because of their essential role in the drug design process. The structure-activity relationships of the most active and promising synthetic modulators are discussed.
Chemical biology & drug design, 2012
In S-acylcysteines and homocysteines, the efficacy and rate of S fi N-acyl transfer (5 and 6 cycl... more In S-acylcysteines and homocysteines, the efficacy and rate of S fi N-acyl transfer (5 and 6 cyclic TSs) vary with the size of S-acyl group. Conformational and quantum chemical calculations indicate that the spatial distance, b(N-C), between the terminal amine and the thioester carbon is shortened by a-C(O)X (X = OH, OMe, NH 2 ) substituents.
A novel anil compounds, 1-{(Z)-[(3,5dimethylphenyl)imino]methyl}naphthalen-2-ol (HNMA) and 5-(die... more A novel anil compounds, 1-{(Z)-[(3,5dimethylphenyl)imino]methyl}naphthalen-2-ol (HNMA) and 5-(diethylamino)-2-{(Z)-[(3,5-dimethylphenyl)imino] methyl} phenol (DMSMA), were prepared and characterized on the basis of elemental analyses, X-ray, 1 H NMR, 13 C NMR, UV–Vis and IR spectral data. Their inhibiting performance for mild steel in 0.5 M H 2 SO 4 solution was evaluated by a series of techniques including potentiodynamic polarization, electrochemical impedance spectroscopy, scanning electronic microscope (SEM), energy-dispersive X-ray spectroscopy (EDX) and theoretical calculations. Findings show that HNMA and DMSMA act as good inhibitors, and their inhibition efficiency increases with increasing their concentration. Polarization data suggested that the Schiff bases molecules used as mixed type inhibitors. Impedance measurements indicating that the corrosion reaction is controlled by charge transfer process. The ad-sorption of HNMA and DMSMA on the metal surface was found to obey Langmuir adsorption isotherm. Furthermore , theoretical study gives insightful explanations of the inhibition mechanism.
Nature Communications, 2014
Synthetic drug-like molecules that directly modulate the activity of key clock proteins offer the... more Synthetic drug-like molecules that directly modulate the activity of key clock proteins offer the potential to directly modulate the endogenous circadian rhythm and treat diseases associated with clock dysfunction. Here we demonstrate that synthetic ligands targeting a key component of the mammalian clock, the nuclear receptors REV-ERBα and β, regulate sleep architecture and emotional behaviour in mice. REV-ERB agonists induce wakefulness and reduce REM and slow-wave sleep. Interestingly, REV-ERB agonists also reduce anxiety-like behaviour. These data are consistent with increased anxiety-like behaviour of REV-ERBβ-null mice, in which REV-ERB agonists have no effect. These results indicate that pharmacological targeting of REV-ERB may lead to the development of novel therapeutics to treat sleep disorders and anxiety.
![Research paper thumbnail of Regioselective synthesis, stereochemical structure, spectroscopic characterization and geometry optimization of dispiro[3H-indole-3,2′-pyrrolidine-3′,3″-piperidines]](https://attachments.academia-assets.com/51081466/thumbnails/1.jpg)
](Journal of Molecular Structure, 2014
Journal of Electroanalytical Chemistry, 2015
RSC Advances, 2011
Enantiopure N-(Cbz, Fmoc, Boc, or Ac)-1H-1,2,4-triazole-(8a-p, and 8f 0 ) and previously unknown ... more Enantiopure N-(Cbz, Fmoc, Boc, or Ac)-1H-1,2,4-triazole-(8a-p, and 8f 0 ) and previously unknown N-Cbz-1,2,4-triazine-derived a-amino acids (11a-d, 11d 0 , 13a,b, and 13a 0 ) were synthesized using microwave irradiation. Reaction conditions led unexpectedly to simultaneous cyclization, deprotection and acetylation of N-Boc-aminoacylamidrazones 7m,n to afford N-acetyl-1H-1,2,4-triazoles 8o,p.
Tetrahedron Letters, 2011
a b s t r a c t GFP chromophore analogs (7a-e, 8, and 10a,b) containing 2-thienyl-, 5-methyl-2-fu... more a b s t r a c t GFP chromophore analogs (7a-e, 8, and 10a,b) containing 2-thienyl-, 5-methyl-2-furyl-, 2-pyrryl, and 6methyl-2-pyridyl-groups were synthesized and their fluorescence spectra recorded in the pH range 1-7. NMR studies showed that protonation of 8 (2-thienyl system) inhibited photoisomerization (Z-E) about the exocyclic double bond but that protonation of 7c (E + Z) (2-pyrryl system) gave only 7cE. Fluorescence studies revealed enhancement of fluorescence intensity of 7c and 7b,e (furyl system) below pH 2.5 and gave a similar result for 10a (pyridyl system) below pH 6. Quantum yields at pH 1 were low, probably due to excited state proton transfer (ESPT).
Tetrahedron, 2007
Reactions of readily available and stable 1-(α-alkoxyalkyl)benzotriazoles type 9a,b and 10a−d wit... more Reactions of readily available and stable 1-(α-alkoxyalkyl)benzotriazoles type 9a,b and 10a−d with a variety of silyl enol ethers 11 or 1,3-dicarbonyl compounds 13 give the expected ketones 12a−l (60−92%), β-keto esters 14a,b (62−67%), and malonates 14c,d (79−88%) in which a tetrahydrofuran or tetrahydropyran moiety has been introduced at the α position. 1-(Benzotriazol-1-yl)alkyl esters 7 are converted by cyanide anion into cyanohydrin esters 15a−i (55−98%).
![Research paper thumbnail of Synthesis of Benzoxazines, Quinazolines and 4H-Benzo[e][1,3]thiazine by ANRORC Rearrangements of 1,2,4-Oxadiazoles](https://attachments.academia-assets.com/50923216/thumbnails/1.jpg)
](Synthesis, 2012
1,2,4-Oxadiazoles undergo ANRORC (addition of nucleophile, ring-opening and ring-closure) rearran... more 1,2,4-Oxadiazoles undergo ANRORC (addition of nucleophile, ring-opening and ring-closure) rearrangements upon reaction with excess of n-butyllithium to give benzoxazines, benzothiazines, and quinazolines in good yields under mild conditions.
Organic & Biomolecular Chemistry, 2010
Conformational equilibria in novel C-nitroso derivatives of indolizines and 3-and 5-azaindolizine... more Conformational equilibria in novel C-nitroso derivatives of indolizines and 3-and 5-azaindolizines have been studied by NMR. 13 C chemical shifts of the carbon alpha to the nitroso group confirmed that these compounds are present in solution as monomers. The conformers arising from restricted rotation about the C-NO bond in monomers were identified by the chemical shifts of the carbon beta to the nitroso group. Barriers to rotation in these compounds were unusually high, particularly for substituents in position 3 of indolizine. Ethyl 2-(methylamino)-1-nitrosoindolizine-3-carboxylate displayed conformers arising from the restricted rotation about the C-COOR bond. Molecular modelling demonstrated that in 1-nitrosoindolizines, the position of the conformational equilibrium is due to steric effects, while for 3-nitrosoindolizines electronic effects prevail. † Electronic supplementary information (ESI) available: Syntheses of Cnitrosoheterocycles 1-7 and the details of the NMR spectroscopy. See
Organic & Biomolecular Chemistry, 2009
2-Hydrazono-3-phenylquinazolin-4(3H)-ones 11a-i are shown by (15)N NMR to exist in DMSO solution ... more 2-Hydrazono-3-phenylquinazolin-4(3H)-ones 11a-i are shown by (15)N NMR to exist in DMSO solution predominantly as the imino tautomers B and not the amino tautomers A. 2-Hydrazino-benzimidazole derivative 12 and 2-hydrazino-4,6-dimethylpyrimidine derivative 13 were found to exist predominantly as the amino tautomers.
MedChemComm, 2012
Enantiopure N-(Cbz, Fmoc, Boc, or Ac)-1H-1,2,4-triazole-(8a-p, and 8f 0 ) and previously unknown ... more Enantiopure N-(Cbz, Fmoc, Boc, or Ac)-1H-1,2,4-triazole-(8a-p, and 8f 0 ) and previously unknown N-Cbz-1,2,4-triazine-derived a-amino acids (11a-d, 11d 0 , 13a,b, and 13a 0 ) were synthesized using microwave irradiation. Reaction conditions led unexpectedly to simultaneous cyclization, deprotection and acetylation of N-Boc-aminoacylamidrazones 7m,n to afford N-acetyl-1H-1,2,4-triazoles 8o,p.
Magnetic Resonance in Chemistry, 2010
The Journal of Organic Chemistry, 2009
N-(Acyl)-1H-benzotriazoles 6a-f react with l-cysteine 5 at 20 degrees C to give exclusively (i) N... more N-(Acyl)-1H-benzotriazoles 6a-f react with l-cysteine 5 at 20 degrees C to give exclusively (i) N-acyl-l-cysteines 8a-e in the presence of triethylamine in CH(3)CN-H(2)O (3:1), but (ii) S-acyl-l-cysteines 7a-e in CH(3)CN-H(2)O (5:1) in the absence of base. Structures 7b, 7d and 8b, 8d are supported by 2D NMR spectroscopic methods including gDQCOSY, gHMQC, gHMBC, and (1)H-(15)N CIGAR-gHMBC experiments. The structure of compound 8d was also supported by single-crystal X-ray diffraction.
RSC Advances
4-Isopropyl–thiotropolone was identified as a novel anti-microbial agent with good therapeutic in... more 4-Isopropyl–thiotropolone was identified as a novel anti-microbial agent with good therapeutic index and ADME properties.
Protection of Metals and Physical Chemistry of Surfaces
Three novel inhibitors based on 4,5,6,7-tetrahydrobenzo[b]thiophene scaffold were synthesized and... more Three novel inhibitors based on 4,5,6,7-tetrahydrobenzo[b]thiophene scaffold were synthesized and characterized. The inhibitive action of the synthesized inhibitors toward carbon steel acid corrosion was investigated using weight loss and polarization techniques. It was found that the three compounds act as good corrosion inhibitor for carbon steel in the acidic medium. The inhibition efficiency was found to increase with increasing concentration and decreased with increasing temperature. The adsorption of inhibitors molecules on the carbon steel surface follows Langmuir adsorption isotherm. The correlation between the inhibitors structures and their corrosion inhibition action was studied by quantum chemical calculations.
Current Pharmaceutical Design
BACKGROUND Hepatitis C virus (HCV) infection poses a considerable threat to the public health. Th... more BACKGROUND Hepatitis C virus (HCV) infection poses a considerable threat to the public health. The current standard of care treatment with pegylated interferon-alpha in combination with ribavirin (PEG-IFN- α+RBV) is associated with significant side effects, poorly tolerated, and provides limited efficacy. The development of direct-acting antiviral agents (DAAs) targeting key viral enzymes essential for viral replication represents a significant milestone in the treatment of chronic HCV infection. Given its critical role in the viral polyprotein processing and the evasion of the host innate immunity, the NS3/4A protease has emerged as a promising drug target for the development of anti-HCV therapies. Although several potent NS3/4A protease inhibitors (PIs) have been approved or are in clinical development, the majority of currently available PIs have significant limitations related to untoward adverse events and a lack of pan-genotypic activity, indicating a continuing unmet medical need for the development and optimization of novel PIs with improved efficacy and tolerability, convenient dosing schedules, and shorter treatment durations. METHODS The inhibitory efficacy of four computer-designed chemically-synthesized compounds was evaluated against in vitro-expressed NS3/4A protease from HCV genotype 4a, the most prevalent genotype in Egypt, using a fluorescence-based enzymatic assay. RESULTS We successfully identified two non-macrocyclic small molecules, BE113 (7a) and BE114 (7b), which exhibited inhibitory activity against HCV NS3/4A protease from HCV genotype 4a. CONCLUSION The two compounds presented in this study may be promising inhibitors against NS3/4A protease of HCV genotype 4a and could be novel lead compounds for developing new therapeutics for the treatment of chronic HCV infection.
Journal of Medicinal Chemistry
Nuclear hormone receptors represent a large family of ligand-activated transcription factors that... more Nuclear hormone receptors represent a large family of ligand-activated transcription factors that include steroid receptors, thyroid/retinoid receptors, and orphan receptors. Among nuclear hormone receptors, the liver X receptors have emerged as very important drug targets. These receptors regulate some of the most important metabolic functions, and they were also identified as anti-inflammatory transcription factors and regulators of the immune system. The development of drugs targeting liver X receptors continues to be a challenge, but advances in our knowledge of receptor structure and function move us forward, toward achieving this goal. This review highlights the latest advances in the development of synthetic LXR modulators in the primary literature from 2013 to 2017. In this review, we place great emphasis on the structure and function of LXRs because of their essential role in the drug design process. The structure-activity relationships of the most active and promising synthetic modulators are discussed.
Chemical biology & drug design, 2012
In S-acylcysteines and homocysteines, the efficacy and rate of S fi N-acyl transfer (5 and 6 cycl... more In S-acylcysteines and homocysteines, the efficacy and rate of S fi N-acyl transfer (5 and 6 cyclic TSs) vary with the size of S-acyl group. Conformational and quantum chemical calculations indicate that the spatial distance, b(N-C), between the terminal amine and the thioester carbon is shortened by a-C(O)X (X = OH, OMe, NH 2 ) substituents.
A novel anil compounds, 1-{(Z)-[(3,5dimethylphenyl)imino]methyl}naphthalen-2-ol (HNMA) and 5-(die... more A novel anil compounds, 1-{(Z)-[(3,5dimethylphenyl)imino]methyl}naphthalen-2-ol (HNMA) and 5-(diethylamino)-2-{(Z)-[(3,5-dimethylphenyl)imino] methyl} phenol (DMSMA), were prepared and characterized on the basis of elemental analyses, X-ray, 1 H NMR, 13 C NMR, UV–Vis and IR spectral data. Their inhibiting performance for mild steel in 0.5 M H 2 SO 4 solution was evaluated by a series of techniques including potentiodynamic polarization, electrochemical impedance spectroscopy, scanning electronic microscope (SEM), energy-dispersive X-ray spectroscopy (EDX) and theoretical calculations. Findings show that HNMA and DMSMA act as good inhibitors, and their inhibition efficiency increases with increasing their concentration. Polarization data suggested that the Schiff bases molecules used as mixed type inhibitors. Impedance measurements indicating that the corrosion reaction is controlled by charge transfer process. The ad-sorption of HNMA and DMSMA on the metal surface was found to obey Langmuir adsorption isotherm. Furthermore , theoretical study gives insightful explanations of the inhibition mechanism.
Nature Communications, 2014
Synthetic drug-like molecules that directly modulate the activity of key clock proteins offer the... more Synthetic drug-like molecules that directly modulate the activity of key clock proteins offer the potential to directly modulate the endogenous circadian rhythm and treat diseases associated with clock dysfunction. Here we demonstrate that synthetic ligands targeting a key component of the mammalian clock, the nuclear receptors REV-ERBα and β, regulate sleep architecture and emotional behaviour in mice. REV-ERB agonists induce wakefulness and reduce REM and slow-wave sleep. Interestingly, REV-ERB agonists also reduce anxiety-like behaviour. These data are consistent with increased anxiety-like behaviour of REV-ERBβ-null mice, in which REV-ERB agonists have no effect. These results indicate that pharmacological targeting of REV-ERB may lead to the development of novel therapeutics to treat sleep disorders and anxiety.
Journal of Molecular Structure, 2014
Journal of Electroanalytical Chemistry, 2015
RSC Advances, 2011
Enantiopure N-(Cbz, Fmoc, Boc, or Ac)-1H-1,2,4-triazole-(8a-p, and 8f 0 ) and previously unknown ... more Enantiopure N-(Cbz, Fmoc, Boc, or Ac)-1H-1,2,4-triazole-(8a-p, and 8f 0 ) and previously unknown N-Cbz-1,2,4-triazine-derived a-amino acids (11a-d, 11d 0 , 13a,b, and 13a 0 ) were synthesized using microwave irradiation. Reaction conditions led unexpectedly to simultaneous cyclization, deprotection and acetylation of N-Boc-aminoacylamidrazones 7m,n to afford N-acetyl-1H-1,2,4-triazoles 8o,p.
Tetrahedron Letters, 2011
a b s t r a c t GFP chromophore analogs (7a-e, 8, and 10a,b) containing 2-thienyl-, 5-methyl-2-fu... more a b s t r a c t GFP chromophore analogs (7a-e, 8, and 10a,b) containing 2-thienyl-, 5-methyl-2-furyl-, 2-pyrryl, and 6methyl-2-pyridyl-groups were synthesized and their fluorescence spectra recorded in the pH range 1-7. NMR studies showed that protonation of 8 (2-thienyl system) inhibited photoisomerization (Z-E) about the exocyclic double bond but that protonation of 7c (E + Z) (2-pyrryl system) gave only 7cE. Fluorescence studies revealed enhancement of fluorescence intensity of 7c and 7b,e (furyl system) below pH 2.5 and gave a similar result for 10a (pyridyl system) below pH 6. Quantum yields at pH 1 were low, probably due to excited state proton transfer (ESPT).
Tetrahedron, 2007
Reactions of readily available and stable 1-(α-alkoxyalkyl)benzotriazoles type 9a,b and 10a−d wit... more Reactions of readily available and stable 1-(α-alkoxyalkyl)benzotriazoles type 9a,b and 10a−d with a variety of silyl enol ethers 11 or 1,3-dicarbonyl compounds 13 give the expected ketones 12a−l (60−92%), β-keto esters 14a,b (62−67%), and malonates 14c,d (79−88%) in which a tetrahydrofuran or tetrahydropyran moiety has been introduced at the α position. 1-(Benzotriazol-1-yl)alkyl esters 7 are converted by cyanide anion into cyanohydrin esters 15a−i (55−98%).
Synthesis, 2012
1,2,4-Oxadiazoles undergo ANRORC (addition of nucleophile, ring-opening and ring-closure) rearran... more 1,2,4-Oxadiazoles undergo ANRORC (addition of nucleophile, ring-opening and ring-closure) rearrangements upon reaction with excess of n-butyllithium to give benzoxazines, benzothiazines, and quinazolines in good yields under mild conditions.
Organic & Biomolecular Chemistry, 2010
Conformational equilibria in novel C-nitroso derivatives of indolizines and 3-and 5-azaindolizine... more Conformational equilibria in novel C-nitroso derivatives of indolizines and 3-and 5-azaindolizines have been studied by NMR. 13 C chemical shifts of the carbon alpha to the nitroso group confirmed that these compounds are present in solution as monomers. The conformers arising from restricted rotation about the C-NO bond in monomers were identified by the chemical shifts of the carbon beta to the nitroso group. Barriers to rotation in these compounds were unusually high, particularly for substituents in position 3 of indolizine. Ethyl 2-(methylamino)-1-nitrosoindolizine-3-carboxylate displayed conformers arising from the restricted rotation about the C-COOR bond. Molecular modelling demonstrated that in 1-nitrosoindolizines, the position of the conformational equilibrium is due to steric effects, while for 3-nitrosoindolizines electronic effects prevail. † Electronic supplementary information (ESI) available: Syntheses of Cnitrosoheterocycles 1-7 and the details of the NMR spectroscopy. See
Organic & Biomolecular Chemistry, 2009
2-Hydrazono-3-phenylquinazolin-4(3H)-ones 11a-i are shown by (15)N NMR to exist in DMSO solution ... more 2-Hydrazono-3-phenylquinazolin-4(3H)-ones 11a-i are shown by (15)N NMR to exist in DMSO solution predominantly as the imino tautomers B and not the amino tautomers A. 2-Hydrazino-benzimidazole derivative 12 and 2-hydrazino-4,6-dimethylpyrimidine derivative 13 were found to exist predominantly as the amino tautomers.
MedChemComm, 2012
Enantiopure N-(Cbz, Fmoc, Boc, or Ac)-1H-1,2,4-triazole-(8a-p, and 8f 0 ) and previously unknown ... more Enantiopure N-(Cbz, Fmoc, Boc, or Ac)-1H-1,2,4-triazole-(8a-p, and 8f 0 ) and previously unknown N-Cbz-1,2,4-triazine-derived a-amino acids (11a-d, 11d 0 , 13a,b, and 13a 0 ) were synthesized using microwave irradiation. Reaction conditions led unexpectedly to simultaneous cyclization, deprotection and acetylation of N-Boc-aminoacylamidrazones 7m,n to afford N-acetyl-1H-1,2,4-triazoles 8o,p.
Magnetic Resonance in Chemistry, 2010
The Journal of Organic Chemistry, 2009
N-(Acyl)-1H-benzotriazoles 6a-f react with l-cysteine 5 at 20 degrees C to give exclusively (i) N... more N-(Acyl)-1H-benzotriazoles 6a-f react with l-cysteine 5 at 20 degrees C to give exclusively (i) N-acyl-l-cysteines 8a-e in the presence of triethylamine in CH(3)CN-H(2)O (3:1), but (ii) S-acyl-l-cysteines 7a-e in CH(3)CN-H(2)O (5:1) in the absence of base. Structures 7b, 7d and 8b, 8d are supported by 2D NMR spectroscopic methods including gDQCOSY, gHMQC, gHMBC, and (1)H-(15)N CIGAR-gHMBC experiments. The structure of compound 8d was also supported by single-crystal X-ray diffraction.