In the present study two new series of 4-[4-(3-hydroxypropoxy)-3-methoxybenzylidene]-1-(3-chlorop... more In the present study two new series of 4-[4-(3-hydroxypropoxy)-3-methoxybenzylidene]-1-(3-chlorophenyl)-2-(alkylthio)-1H-imidazol-5(4H)-ones and 5-[4-(3-hydroxypropoxy)-3-methoxybenzylidene]-3-cyclohexyl-1-(substituted aminomethyl)-2-thioxoimidazolidin-4-ones were synthesized by S-alkylation with some halogenated acyclic hydrocarbons and by a three-component Mannich reaction (MCR), respectively. Both S-alkylated 2-thiohydantoins and Mannich bases were characterized by IR, NMR, mass spectral data, and elemental analysis.
A series of heterocyclic derivatives including 1,2,4-triazole-3(4H)-one (3a,b), 1H-pyrazol-5(4H)-... more A series of heterocyclic derivatives including 1,2,4-triazole-3(4H)-one (3a,b), 1H-pyrazol-5(4H)-one (4,5), 1H-pyrazol-4-carbonitrile (7), pyridine-3-carbonitrile (8, 9a,b), pyrimidine-5-carbonitrile (10a,b), methylpyrimidin-2(1H)-one or thione (11a,b), pyrimidine-5-carboxylate (12a,b), quinazolin-5(6H)-one (13a,b) and indeno [1,2-d] pyrimidin-5-one (14a,b) moieties conjugated with 1,3-disubstituted pyrazole moiety were synthesized on reaction with semicarbazide, thiosemicarbazide, 3-amino-5-oxo-2-pyrazoline, cyanoacetohydrazide, 2-acetyl thiophene, p-chloroacetophenone, urea, thiourea and 1,3-dicarbonyl compounds, respectively, by using 1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazole-4-carboxaldehyde (2) as starting material. The structures of all the newly synthesized products have been established on the basis of analytical and spectral data. The anti-inflammatory screening showed that most of the obtained compounds were found to have significant anti-inflammatory activities with prostaglandin inhibition at a dose level of 2.5 and 5 mg/kg comparable to celecoxib as a reference control. The ulcer indices of all compounds are mainly in the safe level (UI = 2.10-4.27) except for compounds 9a and 14a, which were highly ulcerogenic.
Quinolines and its derivatives represent a broad class of compounds, which have received consider... more Quinolines and its derivatives represent a broad class of compounds, which have received considerable attention due to their wide range of pharmacological properties such as, anti-inflammatory, COX inhibitor, anticancer and analgesic. Starting from 2-phenylquinoline-4-carbohydrazide, several new 2phenylquinoline-4-carboxamide derivatives were synthesized, characterized and screened for their analgesic and anti-inflammatory activity using peripheral analgesic activity (writhing test) and carrageenan-induced paw edema test in rats. Among these derivatives, compound 5 linked nucleoside analogue showed significant anti-inflammatory activity as that of diclofenac sodium (reference drug) in animal models of inflammation.
Starting from l,6-diamino-3,5-dicyano-4-aryl-2-pyridones, substituted triazolo[l,5-a]pyridines an... more Starting from l,6-diamino-3,5-dicyano-4-aryl-2-pyridones, substituted triazolo[l,5-a]pyridines and 1,8-naphthyridine derivatives have been synthesized. All the synthesized compounds were fully characterized by spectroscopic, physical data, and elemental analyses. Some of triazolo[l,5-a]pyridines were tested with respect to their analgesic and anti-inflammatory activities. All tested compounds exhibited analgesic activities comparable or superior to Valdecoxib. The anti-inflammatory activity was present in all the tested compounds as well and exceeded that of Hydrocortisone.
ABSTRACT Some novel bicyclic thiazolopyrimidine derivatives bearing various substituents have bee... more ABSTRACT Some novel bicyclic thiazolopyrimidine derivatives bearing various substituents have been synthesized through one-pot three-component method. Structures of the target compounds were confirmed by elemental analysis and spectral data. Some selected members of the newly synthesized compounds were investigated for their analgesic and anti-inflammatory activities and revealed pronounced anti-inflammatory activity greater than that of indomethacin (reference drug).
Ketorolac (KC) suffers from the general side effects of NSAIDs, owing to presence of free carboxy... more Ketorolac (KC) suffers from the general side effects of NSAIDs, owing to presence of free carboxylic acid group. The study aimed to retard the adverse effects of gastrointestinal origin. Ten prodrugs of KC were synthesized by amidation with ethyl esters of amino acids, namely, glycine, L-phenylalanine, L-tryptophan, L-valine, L-isoleucine, L-alanine, L-leucine, L-glutamic acid, L-aspartic acid and b-alanine. Purified synthesized prodrugs were characterized by m.p., TLC, solubility, partition coefficients, elemental analyses, UV, FTIR, NMR and MS. Synthesized prodrugs were subjected for biopharmaceutical studies, analgesic, anti-inflammatory activities and ulcerogenic index. Marked reduction of ulcerogenic index and comparable analgesic, anti-inflammatory activities were obtained in all cases as compared to KC. Among synthesized prodrugs, viz. AR-11, AR-19 and AR-20 showed excellent pharmacological response and encouraging hydrolysis rate both in SIF and in 80% human plasma. Prodrugs with increased aliphatic side chain length or introduction of aromatic substituent showed enhanced partition coefficient but diminished dissolution and hydrolysis rates. Such prodrugs can be considered for sustained release purpose.
A new series of pyrido[2,3-d]pyrimidones incorporated pyrazoles and fused triazoles are synthesiz... more A new series of pyrido[2,3-d]pyrimidones incorporated pyrazoles and fused triazoles are synthesized and tested in vitro for cytotoxic effect against cancer cell lines: HePG-2, HCT-116, MCF-7, PC-3, and A-549. Their inhibition of protein kinase is assessed. The highest growth inhibitory (IC 50 0.3 μM) effect is determined for one of compounds as compared with doxorubicin (IC 50 0.6 μM). A modeling study is performed for approaching the compounds mode of binding and their similarity with the positive control drugs.
Absract-Novel polycyclic compounds, 1-pyrene-based pyridone derivatives, are synthesized by treat... more Absract-Novel polycyclic compounds, 1-pyrene-based pyridone derivatives, are synthesized by treatment of pyrenyl acetohydtazide with several arylidenemalononitriles and acetylacetone. Intramolecular cyclization furnishes the functionalized substituted pyridine-2-ones with high yields. Structures of the products are elucidated from the spectral data. Tests on antibacterial activity of the products reveal their high antibacterial effect.
A series of octa bridged peptide and macrocyclic pentapeptide Schiff base derivatives were synthe... more A series of octa bridged peptide and macrocyclic pentapeptide Schiff base derivatives were synthesized from tetrapeptide hydrazide and macrocyclic pentapeptide ester. Condensation of hydrazide with acid anhydrides upon refluxing in acetic acid afforded the corresponding 3,5-bis-tetraimide pyridine and macrocyclic octapeptide derivatives. Treatment of macrocyclic pentapeptide ester with hydrazine hydrate gave the corresponding acid hydrazide derivative. Condensation of the latter with aromatic aldehydes led to the corresponding cyclic pentapeptide Schiff bases.
A novel compounds of 4,6-diaryl-2-oxo(imino)-1,2-dihydro-pyridine-3-carbonitriles has been synthe... more A novel compounds of 4,6-diaryl-2-oxo(imino)-1,2-dihydro-pyridine-3-carbonitriles has been synthesized by reaction of 1-(3-chlorophenyl)-3-(pyren-1-yl)-1H-pyrazole-4-carbaldehyde with different 1-(substituted phenyl)ethanones and ethyl cyanoacetate or malononitrile in presence of ammonium acetate. Structure of the newly synthesized compounds was elucidated from chemical and spectroscopic data.
A series of novel 1,8-naphthyridine derivatives containing Schiff bases and amino substituents we... more A series of novel 1,8-naphthyridine derivatives containing Schiff bases and amino substituents were synthesized starting from the reaction of 4-hydrazinyl-2,7-dimethyl-1,8-naphthyridine with different active carbonyl groups, acid monoanhydrides and tetracarboxylic acid anhydrides. Structures of new compounds were elucidated by means of physical and spectroscopic analyses.
A series of novel 2-thioxoimidazolidine glycosides were prepared via reaction of the key intermed... more A series of novel 2-thioxoimidazolidine glycosides were prepared via reaction of the key intermediate 2-(benzylsulfanyl)-5-[4-(3-hydroxypropoxy)-3-(methoxybenzylidene)]-3-phenyl-1H-imidazol-4-one with different sugar aldose or sugar hydrazones to give the corresponding glycosides. The newly synthesized compounds were confirmed by physical and spectral data.
Some novel (E)-2-cyano-3-(substituted phenyl/dimethylamino)-N'-[1-(pyren-3-yl)]acrylohydrazides a... more Some novel (E)-2-cyano-3-(substituted phenyl/dimethylamino)-N'-[1-(pyren-3-yl)]acrylohydrazides and benzochromenone-2-carbohydrazide derivatives were synthesized by reaction of (E)-2-cyano-N'-[1-(pyren-3-yl)ethylidene]acetohydrazide with several reagents. Chemical structures of the newly obtained products were determined by elemental and spectroscopic analysis.
Imidazole derivatives Imidazole derivatives R 0190 Synthesis and Antimicrobial Activities of Some... more Imidazole derivatives Imidazole derivatives R 0190 Synthesis and Antimicrobial Activities of Some Imidazole Substituted Indoles.-Compounds (III) show antibacterial activity, with compound (IIIe) being the most effective. In contrast, compound (Va) shows antifungal activity.
Phosphorus Sulfur and Silicon and The Related Elements, Nov 3, 2008
A series of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)p~rolidin-2-ones was synthesized and evalua... more A series of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)p~rolidin-2-ones was synthesized and evaluated as candidate antiinflammatoryfanalgesic agents as well as dual inhibitors of prostaglandin and leukotriene synthesis. Some compounds that showed dual inhibitory activity were found to possess equipotent antiinflammatory activities to indomethacin, with reduced ulcerogenic effects. One of the compounds, N-methoxy-3-(3,5-di-tert-butyl-4hydroxybenzylidene)pyrrolidin-2-one, was found to have a wider safety margin than indomethacin or piroxicam, and was selected for detailed evaluation as a candidate drug for clinical application.
In order the study normal flora, the samples were collected from non infected individuals. In ord... more In order the study normal flora, the samples were collected from non infected individuals. In order the study the causative agents, the sample were collected form infected individuals. Sample was processed both macroscopically and microscopically. The results revealed that the normal flora of throat of individuals without throat infections (14 specimens) were Staphylococus aureus. Among 110 specimens collected from individuals with throat infections, 47 were positive for Staphylococcus aureus and 12 were positive were positive for Staphylococcus epidermidis. And among the remaining specimens, 39 were Pseumonas aeruginosa, 6 were Proteus mirabilis, 4 were Klebsiella pneumoniae and 2 were gram positive cocci in chains (Streptococci). All bacteria were tested for their susceptibility to different antibiotics. Among 47 Staphylococcus aureus, 33 were sensitive to penicillin and 14 were resistant. Fungus such as Candida albicans, Candida tropicalis and Aspergillus niger were isolated and identified. This kind of infection reflects the immunodeficiency of the individuals.
Bulletin of the Chemical Society of Ethiopia, 2019
A group of trisubstituted pyrazoles containing thiophen, 2-alkyloxypyridine and thieno[2,3d]pyrim... more A group of trisubstituted pyrazoles containing thiophen, 2-alkyloxypyridine and thieno[2,3d]pyrimidine heterocycles were synthesized in a study for possible analgesic agents. The desired products were obtained by reaction of 2-((1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazol-4-yl)methylene)malononitrile with sulfur in presence of TEA, followed by treatment with different reagents. Newer products were examined for their analgesic properties, among them, analog 7 showed significant analgesic effects in comparison with reference medicines activity.
In the present study two new series of 4-[4-(3-hydroxypropoxy)-3-methoxybenzylidene]-1-(3-chlorop... more In the present study two new series of 4-[4-(3-hydroxypropoxy)-3-methoxybenzylidene]-1-(3-chlorophenyl)-2-(alkylthio)-1H-imidazol-5(4H)-ones and 5-[4-(3-hydroxypropoxy)-3-methoxybenzylidene]-3-cyclohexyl-1-(substituted aminomethyl)-2-thioxoimidazolidin-4-ones were synthesized by S-alkylation with some halogenated acyclic hydrocarbons and by a three-component Mannich reaction (MCR), respectively. Both S-alkylated 2-thiohydantoins and Mannich bases were characterized by IR, NMR, mass spectral data, and elemental analysis.
A series of heterocyclic derivatives including 1,2,4-triazole-3(4H)-one (3a,b), 1H-pyrazol-5(4H)-... more A series of heterocyclic derivatives including 1,2,4-triazole-3(4H)-one (3a,b), 1H-pyrazol-5(4H)-one (4,5), 1H-pyrazol-4-carbonitrile (7), pyridine-3-carbonitrile (8, 9a,b), pyrimidine-5-carbonitrile (10a,b), methylpyrimidin-2(1H)-one or thione (11a,b), pyrimidine-5-carboxylate (12a,b), quinazolin-5(6H)-one (13a,b) and indeno [1,2-d] pyrimidin-5-one (14a,b) moieties conjugated with 1,3-disubstituted pyrazole moiety were synthesized on reaction with semicarbazide, thiosemicarbazide, 3-amino-5-oxo-2-pyrazoline, cyanoacetohydrazide, 2-acetyl thiophene, p-chloroacetophenone, urea, thiourea and 1,3-dicarbonyl compounds, respectively, by using 1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazole-4-carboxaldehyde (2) as starting material. The structures of all the newly synthesized products have been established on the basis of analytical and spectral data. The anti-inflammatory screening showed that most of the obtained compounds were found to have significant anti-inflammatory activities with prostaglandin inhibition at a dose level of 2.5 and 5 mg/kg comparable to celecoxib as a reference control. The ulcer indices of all compounds are mainly in the safe level (UI = 2.10-4.27) except for compounds 9a and 14a, which were highly ulcerogenic.
Quinolines and its derivatives represent a broad class of compounds, which have received consider... more Quinolines and its derivatives represent a broad class of compounds, which have received considerable attention due to their wide range of pharmacological properties such as, anti-inflammatory, COX inhibitor, anticancer and analgesic. Starting from 2-phenylquinoline-4-carbohydrazide, several new 2phenylquinoline-4-carboxamide derivatives were synthesized, characterized and screened for their analgesic and anti-inflammatory activity using peripheral analgesic activity (writhing test) and carrageenan-induced paw edema test in rats. Among these derivatives, compound 5 linked nucleoside analogue showed significant anti-inflammatory activity as that of diclofenac sodium (reference drug) in animal models of inflammation.
Starting from l,6-diamino-3,5-dicyano-4-aryl-2-pyridones, substituted triazolo[l,5-a]pyridines an... more Starting from l,6-diamino-3,5-dicyano-4-aryl-2-pyridones, substituted triazolo[l,5-a]pyridines and 1,8-naphthyridine derivatives have been synthesized. All the synthesized compounds were fully characterized by spectroscopic, physical data, and elemental analyses. Some of triazolo[l,5-a]pyridines were tested with respect to their analgesic and anti-inflammatory activities. All tested compounds exhibited analgesic activities comparable or superior to Valdecoxib. The anti-inflammatory activity was present in all the tested compounds as well and exceeded that of Hydrocortisone.
ABSTRACT Some novel bicyclic thiazolopyrimidine derivatives bearing various substituents have bee... more ABSTRACT Some novel bicyclic thiazolopyrimidine derivatives bearing various substituents have been synthesized through one-pot three-component method. Structures of the target compounds were confirmed by elemental analysis and spectral data. Some selected members of the newly synthesized compounds were investigated for their analgesic and anti-inflammatory activities and revealed pronounced anti-inflammatory activity greater than that of indomethacin (reference drug).
Ketorolac (KC) suffers from the general side effects of NSAIDs, owing to presence of free carboxy... more Ketorolac (KC) suffers from the general side effects of NSAIDs, owing to presence of free carboxylic acid group. The study aimed to retard the adverse effects of gastrointestinal origin. Ten prodrugs of KC were synthesized by amidation with ethyl esters of amino acids, namely, glycine, L-phenylalanine, L-tryptophan, L-valine, L-isoleucine, L-alanine, L-leucine, L-glutamic acid, L-aspartic acid and b-alanine. Purified synthesized prodrugs were characterized by m.p., TLC, solubility, partition coefficients, elemental analyses, UV, FTIR, NMR and MS. Synthesized prodrugs were subjected for biopharmaceutical studies, analgesic, anti-inflammatory activities and ulcerogenic index. Marked reduction of ulcerogenic index and comparable analgesic, anti-inflammatory activities were obtained in all cases as compared to KC. Among synthesized prodrugs, viz. AR-11, AR-19 and AR-20 showed excellent pharmacological response and encouraging hydrolysis rate both in SIF and in 80% human plasma. Prodrugs with increased aliphatic side chain length or introduction of aromatic substituent showed enhanced partition coefficient but diminished dissolution and hydrolysis rates. Such prodrugs can be considered for sustained release purpose.
A new series of pyrido[2,3-d]pyrimidones incorporated pyrazoles and fused triazoles are synthesiz... more A new series of pyrido[2,3-d]pyrimidones incorporated pyrazoles and fused triazoles are synthesized and tested in vitro for cytotoxic effect against cancer cell lines: HePG-2, HCT-116, MCF-7, PC-3, and A-549. Their inhibition of protein kinase is assessed. The highest growth inhibitory (IC 50 0.3 μM) effect is determined for one of compounds as compared with doxorubicin (IC 50 0.6 μM). A modeling study is performed for approaching the compounds mode of binding and their similarity with the positive control drugs.
Absract-Novel polycyclic compounds, 1-pyrene-based pyridone derivatives, are synthesized by treat... more Absract-Novel polycyclic compounds, 1-pyrene-based pyridone derivatives, are synthesized by treatment of pyrenyl acetohydtazide with several arylidenemalononitriles and acetylacetone. Intramolecular cyclization furnishes the functionalized substituted pyridine-2-ones with high yields. Structures of the products are elucidated from the spectral data. Tests on antibacterial activity of the products reveal their high antibacterial effect.
A series of octa bridged peptide and macrocyclic pentapeptide Schiff base derivatives were synthe... more A series of octa bridged peptide and macrocyclic pentapeptide Schiff base derivatives were synthesized from tetrapeptide hydrazide and macrocyclic pentapeptide ester. Condensation of hydrazide with acid anhydrides upon refluxing in acetic acid afforded the corresponding 3,5-bis-tetraimide pyridine and macrocyclic octapeptide derivatives. Treatment of macrocyclic pentapeptide ester with hydrazine hydrate gave the corresponding acid hydrazide derivative. Condensation of the latter with aromatic aldehydes led to the corresponding cyclic pentapeptide Schiff bases.
A novel compounds of 4,6-diaryl-2-oxo(imino)-1,2-dihydro-pyridine-3-carbonitriles has been synthe... more A novel compounds of 4,6-diaryl-2-oxo(imino)-1,2-dihydro-pyridine-3-carbonitriles has been synthesized by reaction of 1-(3-chlorophenyl)-3-(pyren-1-yl)-1H-pyrazole-4-carbaldehyde with different 1-(substituted phenyl)ethanones and ethyl cyanoacetate or malononitrile in presence of ammonium acetate. Structure of the newly synthesized compounds was elucidated from chemical and spectroscopic data.
A series of novel 1,8-naphthyridine derivatives containing Schiff bases and amino substituents we... more A series of novel 1,8-naphthyridine derivatives containing Schiff bases and amino substituents were synthesized starting from the reaction of 4-hydrazinyl-2,7-dimethyl-1,8-naphthyridine with different active carbonyl groups, acid monoanhydrides and tetracarboxylic acid anhydrides. Structures of new compounds were elucidated by means of physical and spectroscopic analyses.
A series of novel 2-thioxoimidazolidine glycosides were prepared via reaction of the key intermed... more A series of novel 2-thioxoimidazolidine glycosides were prepared via reaction of the key intermediate 2-(benzylsulfanyl)-5-[4-(3-hydroxypropoxy)-3-(methoxybenzylidene)]-3-phenyl-1H-imidazol-4-one with different sugar aldose or sugar hydrazones to give the corresponding glycosides. The newly synthesized compounds were confirmed by physical and spectral data.
Some novel (E)-2-cyano-3-(substituted phenyl/dimethylamino)-N'-[1-(pyren-3-yl)]acrylohydrazides a... more Some novel (E)-2-cyano-3-(substituted phenyl/dimethylamino)-N'-[1-(pyren-3-yl)]acrylohydrazides and benzochromenone-2-carbohydrazide derivatives were synthesized by reaction of (E)-2-cyano-N'-[1-(pyren-3-yl)ethylidene]acetohydrazide with several reagents. Chemical structures of the newly obtained products were determined by elemental and spectroscopic analysis.
Imidazole derivatives Imidazole derivatives R 0190 Synthesis and Antimicrobial Activities of Some... more Imidazole derivatives Imidazole derivatives R 0190 Synthesis and Antimicrobial Activities of Some Imidazole Substituted Indoles.-Compounds (III) show antibacterial activity, with compound (IIIe) being the most effective. In contrast, compound (Va) shows antifungal activity.
Phosphorus Sulfur and Silicon and The Related Elements, Nov 3, 2008
A series of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)p~rolidin-2-ones was synthesized and evalua... more A series of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)p~rolidin-2-ones was synthesized and evaluated as candidate antiinflammatoryfanalgesic agents as well as dual inhibitors of prostaglandin and leukotriene synthesis. Some compounds that showed dual inhibitory activity were found to possess equipotent antiinflammatory activities to indomethacin, with reduced ulcerogenic effects. One of the compounds, N-methoxy-3-(3,5-di-tert-butyl-4hydroxybenzylidene)pyrrolidin-2-one, was found to have a wider safety margin than indomethacin or piroxicam, and was selected for detailed evaluation as a candidate drug for clinical application.
In order the study normal flora, the samples were collected from non infected individuals. In ord... more In order the study normal flora, the samples were collected from non infected individuals. In order the study the causative agents, the sample were collected form infected individuals. Sample was processed both macroscopically and microscopically. The results revealed that the normal flora of throat of individuals without throat infections (14 specimens) were Staphylococus aureus. Among 110 specimens collected from individuals with throat infections, 47 were positive for Staphylococcus aureus and 12 were positive were positive for Staphylococcus epidermidis. And among the remaining specimens, 39 were Pseumonas aeruginosa, 6 were Proteus mirabilis, 4 were Klebsiella pneumoniae and 2 were gram positive cocci in chains (Streptococci). All bacteria were tested for their susceptibility to different antibiotics. Among 47 Staphylococcus aureus, 33 were sensitive to penicillin and 14 were resistant. Fungus such as Candida albicans, Candida tropicalis and Aspergillus niger were isolated and identified. This kind of infection reflects the immunodeficiency of the individuals.
Bulletin of the Chemical Society of Ethiopia, 2019
A group of trisubstituted pyrazoles containing thiophen, 2-alkyloxypyridine and thieno[2,3d]pyrim... more A group of trisubstituted pyrazoles containing thiophen, 2-alkyloxypyridine and thieno[2,3d]pyrimidine heterocycles were synthesized in a study for possible analgesic agents. The desired products were obtained by reaction of 2-((1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazol-4-yl)methylene)malononitrile with sulfur in presence of TEA, followed by treatment with different reagents. Newer products were examined for their analgesic properties, among them, analog 7 showed significant analgesic effects in comparison with reference medicines activity.
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