An antikinetoplastid pharmacomodulation study at position 3 of the recently described hit molecul... more An antikinetoplastid pharmacomodulation study at position 3 of the recently described hit molecule 3-bromo-8-nitroquinolin-2(1H)-one was conducted. Twenty-four derivatives were synthesised using the Suzuki-Miyaura cross-coupling reaction and evaluated in vitro on both Leishmania infantum axenic amastigotes and Trypanosoma brucei brucei trypomastigotes. Introduction of a para-carboxyphenyl group at position 3 of the scaffold led to the selective antitrypanosomal hit molecule 3-(4-carboxyphenyl)-8-nitroquinolin-2(1H)-one (21) with a lower reduction potential (-0.56 V) than the initial hit (-0.45 V). Compound 21 displays micromolar antitrypanosomal activity (IC =1.5 μm) and low cytotoxicity on the human HepG2 cell line (CC =120 μm), having a higher selectivity index (SI=80) than the reference drug eflornithine. Contrary to results previously obtained in this series, hit compound 21 is inactive toward L. infantum and is not efficiently bioactivated by T. brucei brucei type I nitroreduct...
New derivatives of pyrazolo[3,4-]pyrazines and related heterocycles were synthesized using 5-amin... more New derivatives of pyrazolo[3,4-]pyrazines and related heterocycles were synthesized using 5-amino-3-methyl-4-nitroso-1-phenyl-pyrazole () as a starting material. The 5-acetyl derivative was shown to be a useful key intermediate for the synthesis of several derivatives of pyrazolopyrazines. Some of the prepared compounds were evaluated for their anti-inflammatory and anti-breast cancer MCF-7 cell line activities. SAR study showed that compounds and exhibited remarkable anti-inflammatory activity, where showed the same activity as that of the reference drug indomethacin. On the other hand, compounds , showed very significant inhibitory activity ( < 0.001) against MCF-7 breast cancer cell line.
This work presents a second-to-none method for Taxol isolation from the Endophytic fungus Cladosp... more This work presents a second-to-none method for Taxol isolation from the Endophytic fungus Cladosporium sphaerospermum (AUMC 6896) and the Entomopathogenic fungus Metarizium anisopliae (AUMC 5130). The extracts were analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) using positive electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. This is rapid, consistent, reproducible, accurate, and sensitive for quantifying Taxol across multiple samples. The yield of crude Taxol product obtained from Potato Dextrose broth (PDB) medium inoculated with Cladosporium sphaerospermu and Metarizium anisopliae was found to be 3.732, and 0.0023 μg L respectively. The yield can be improved by adding ammonium acetate or salicylic acid to the culture broth. Addition of ammonium acetate (AA) (20 mg L) to culture media resulted in an increase of Taxol yield to 30.365 and 27.289 μg L respectively. Productio...
Manganese(iii) acetate mediated peroxycyclization between 2-hydroxy-3-methylnaphthoquinone and al... more Manganese(iii) acetate mediated peroxycyclization between 2-hydroxy-3-methylnaphthoquinone and alkenes allowed the synthesis of more than 50 original dihydronaphtho[2,3-c][1,2]dioxine-5,10(3H,10aH)-diones.
The synthesis of spiro-γ-amino(or γ-chloro)-β lactams and spiro-4-thiazolidones by the cycloaddit... more The synthesis of spiro-γ-amino(or γ-chloro)-β lactams and spiro-4-thiazolidones by the cycloaddition reaction of 3-isatylidene anil derivatives, phthalylglycyl chloride (or chloroacetyl chloride) and/or mercaptoacetic acid has been investigated. 3-Isatylidene anils were prepared by the reaction of isatine with substituted aniline, a-naphthylamine, 2-aminothiazoles, 2-aminothiadiazoles and 2-aminopyridine, respectively.
ABSTRACT An efficient and versatile synthesis of indane, tetralin and benzosuberan derivatives ha... more ABSTRACT An efficient and versatile synthesis of indane, tetralin and benzosuberan derivatives has been developed; the synthesis starts from nonactivated aromatic compounds bearing unsaturated side chains and is a bismuth(III) or indium(III) trifluoromethanesulfonate-catalysed atom-economic process. A variety of polycyclic compounds have been isolated in high yields. Lactonisation could be observed for esters with 2,2-disubstituted terminal olefins through a Lewis acid catalysed reaction between the olefin and one of the ester groups.
7-Chloromethyl-6-nitro-5H-thiazolo[3,2-a]pyrimidin-5-one (2) is obtained by cyclocondensation of ... more 7-Chloromethyl-6-nitro-5H-thiazolo[3,2-a]pyrimidin-5-one (2) is obtained by cyclocondensation of 2-aminothiazole with ethyl 4-chloroacetoacetate. This product was shown to react with various nitronate or malonate anions under microwave irradiation to give potentially bioactive 6-nitro-5H-thiazolo[3,2-a]pyrimidin-5-ones. Extension to other anions centered on S atom allows for the generalization this synthetic procedure.
ABSTRACT A series of novel pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine substituted at N8 pyraz... more ABSTRACT A series of novel pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine substituted at N8 pyrazole nitrogen and at the 5-amino group was synthesized and their affinities to all four cloned human adenosine receptor subtypes were evaluated by competition binding assays ...
An antikinetoplastid pharmacomodulation study at position 3 of the recently described hit molecul... more An antikinetoplastid pharmacomodulation study at position 3 of the recently described hit molecule 3-bromo-8-nitroquinolin-2(1H)-one was conducted. Twenty-four derivatives were synthesised using the Suzuki-Miyaura cross-coupling reaction and evaluated in vitro on both Leishmania infantum axenic amastigotes and Trypanosoma brucei brucei trypomastigotes. Introduction of a para-carboxyphenyl group at position 3 of the scaffold led to the selective antitrypanosomal hit molecule 3-(4-carboxyphenyl)-8-nitroquinolin-2(1H)-one (21) with a lower reduction potential (-0.56 V) than the initial hit (-0.45 V). Compound 21 displays micromolar antitrypanosomal activity (IC =1.5 μm) and low cytotoxicity on the human HepG2 cell line (CC =120 μm), having a higher selectivity index (SI=80) than the reference drug eflornithine. Contrary to results previously obtained in this series, hit compound 21 is inactive toward L. infantum and is not efficiently bioactivated by T. brucei brucei type I nitroreduct...
New derivatives of pyrazolo[3,4-]pyrazines and related heterocycles were synthesized using 5-amin... more New derivatives of pyrazolo[3,4-]pyrazines and related heterocycles were synthesized using 5-amino-3-methyl-4-nitroso-1-phenyl-pyrazole () as a starting material. The 5-acetyl derivative was shown to be a useful key intermediate for the synthesis of several derivatives of pyrazolopyrazines. Some of the prepared compounds were evaluated for their anti-inflammatory and anti-breast cancer MCF-7 cell line activities. SAR study showed that compounds and exhibited remarkable anti-inflammatory activity, where showed the same activity as that of the reference drug indomethacin. On the other hand, compounds , showed very significant inhibitory activity ( < 0.001) against MCF-7 breast cancer cell line.
This work presents a second-to-none method for Taxol isolation from the Endophytic fungus Cladosp... more This work presents a second-to-none method for Taxol isolation from the Endophytic fungus Cladosporium sphaerospermum (AUMC 6896) and the Entomopathogenic fungus Metarizium anisopliae (AUMC 5130). The extracts were analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) using positive electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. This is rapid, consistent, reproducible, accurate, and sensitive for quantifying Taxol across multiple samples. The yield of crude Taxol product obtained from Potato Dextrose broth (PDB) medium inoculated with Cladosporium sphaerospermu and Metarizium anisopliae was found to be 3.732, and 0.0023 μg L respectively. The yield can be improved by adding ammonium acetate or salicylic acid to the culture broth. Addition of ammonium acetate (AA) (20 mg L) to culture media resulted in an increase of Taxol yield to 30.365 and 27.289 μg L respectively. Productio...
Manganese(iii) acetate mediated peroxycyclization between 2-hydroxy-3-methylnaphthoquinone and al... more Manganese(iii) acetate mediated peroxycyclization between 2-hydroxy-3-methylnaphthoquinone and alkenes allowed the synthesis of more than 50 original dihydronaphtho[2,3-c][1,2]dioxine-5,10(3H,10aH)-diones.
The synthesis of spiro-γ-amino(or γ-chloro)-β lactams and spiro-4-thiazolidones by the cycloaddit... more The synthesis of spiro-γ-amino(or γ-chloro)-β lactams and spiro-4-thiazolidones by the cycloaddition reaction of 3-isatylidene anil derivatives, phthalylglycyl chloride (or chloroacetyl chloride) and/or mercaptoacetic acid has been investigated. 3-Isatylidene anils were prepared by the reaction of isatine with substituted aniline, a-naphthylamine, 2-aminothiazoles, 2-aminothiadiazoles and 2-aminopyridine, respectively.
ABSTRACT An efficient and versatile synthesis of indane, tetralin and benzosuberan derivatives ha... more ABSTRACT An efficient and versatile synthesis of indane, tetralin and benzosuberan derivatives has been developed; the synthesis starts from nonactivated aromatic compounds bearing unsaturated side chains and is a bismuth(III) or indium(III) trifluoromethanesulfonate-catalysed atom-economic process. A variety of polycyclic compounds have been isolated in high yields. Lactonisation could be observed for esters with 2,2-disubstituted terminal olefins through a Lewis acid catalysed reaction between the olefin and one of the ester groups.
7-Chloromethyl-6-nitro-5H-thiazolo[3,2-a]pyrimidin-5-one (2) is obtained by cyclocondensation of ... more 7-Chloromethyl-6-nitro-5H-thiazolo[3,2-a]pyrimidin-5-one (2) is obtained by cyclocondensation of 2-aminothiazole with ethyl 4-chloroacetoacetate. This product was shown to react with various nitronate or malonate anions under microwave irradiation to give potentially bioactive 6-nitro-5H-thiazolo[3,2-a]pyrimidin-5-ones. Extension to other anions centered on S atom allows for the generalization this synthetic procedure.
ABSTRACT A series of novel pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine substituted at N8 pyraz... more ABSTRACT A series of novel pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine substituted at N8 pyrazole nitrogen and at the 5-amino group was synthesized and their affinities to all four cloned human adenosine receptor subtypes were evaluated by competition binding assays ...
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