Eman A. Ragab

Synthesis, anti-HCV, antioxidant, and peroxynitrite inhibitory activity of fused benzosuberone derivatives

Reaction of benzosuberone 1 with dimethylformamide-dimethylacetal (DMF-DMA) gives 2-dimethylamino-methylenebenozosuberone 2 which in turn reacts with heterocyclic amines to furnish new heterocyclic ring systems 6-9. Moreover, enaminone 2 reacts with hydrazine hydrate and hydroxylamine hydrochloride to afford the corresponding benzo[6,7]cyclohepta[1,2-c]pyrazole (10) and benzo[6,7]cyclohepta[2,1-d]isoxazole (12), respectively. In addition, the reactions of enaminone 2 with active methylene compounds afforded benzo[6,7]cyclohepta[1,2-b]pyridines (13-18). The X-ray crystallographic analysis of compounds 6 and 16, were recorded. We demonstrated the ability of nine new synthesized compounds to inhibit Hepatitis C Virus (HCV) and Subacute Sclerosing Panencephalitis (SSPE) due to structural similarity between ribavirin and some of the newly synthesized compounds were they contain triazoles and its bioisosters. In addition, the ability of ten synthesized compounds to react with the biologically relevant reactive nitrogen species, peroxynitrite was investigated indirectly by measurement of their ability to inhibit ONOO(-)-induced tyrosine nitration. The antioxidant activity of these ten compounds was also studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay.

Synthesis and Antimicrobial Evaluation of Some New Cyclooctanones and Cyclooctane-Based Heterocycles

The versatile synthon (E)‐2‐((dimethyl amino)methylene)cyclooctanone (2) was used as a key intermediate for the synthesis of cyclooctanones and cyclooctane‐based heterocycles with pyrazole, isoxazole, pyrimidine, pyrazolopyrimidine, triazolopyrimidine and imidazopyrimidine derivatives via its reactions with several nitrogen nucleophiles. The newly synthesized compounds were screened in vitro for their antimicrobial activity against pathogenic microorganisms (Listeria monocytogenes, methicillin‐resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans). Most of the tested compounds showed moderate to high antibacterial and antifungal effects against the tested pathogenic microorganisms. Among the synthesized compounds, 2‐((p‐sulfonamidophenyl)methylene)cyclooctanone (5) showed excellent activity against Listeria monocytogenes.

A Facile Access to Some New Pyrazole, 1,3,4-Thiadiazole, and Thiophene Derivatives via β-Ketosulfones

3-Bromoacetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile (1) reacts with sodium benzenesulfinate to give the corresponding ketosulfone 2. Treatment of 2 with hydrazonoyl chlorides 3a,b gives the 3,3′-bipyrazoles 5a,b. Ketosulfone 2 reacts also with arylidenemalononitriles to give the pyrazolylpyridones 10a,b. The reaction of compound 2 with phenylisothiocyanate and potassium hydroxide and treating intermediate with hydrazonoyl halides and with α-haloketones gives the 1,3,4-thiadiazoles 18a–c and thiophenes 21a–f, respectively.

Synthesis and Antifungal Activity of Novel Quinazolin-4(3H)-one Derivatives

Abstract A novel group of 6-iodoquinazolin-4(3H)-one derivatives was prepared starting from 6-iodo-2-ethoxy-4H-3,1-benzoxazin-4-one (3) via action of various nitrogen nucleophiles such as primary and secondary amines, hydrazine hydrate, and its derivatives. The 3-amino-2-hydrazinyl-6-iodoquinazolin-4(3H)-one (15) was used as a key starting material to prepare new heterocyclic compounds. The structures of all synthesized compounds were inferred from the infrared, mass spectral, and 1H NMR spectral data as well as elemental analysis. The fungicidal activities of the target compounds were preliminarily evaluated. GRAPHICAL ABSTRACT

Polyheterocyclic ring systems with bridgehead nitrogen atoms: a facile route to some novel Azolo-1,2,4-triazine derivatives

The synthesis of the entitled azolo-1,2,4-triazines via the reaction of some functionalized thiazole derivatives with several heterocyclic diazonium salts is described.

Polyheterocyclic systems incorporating pyrazole, thiophene, thiazole, and thiadiazole moieties

A variety of polyheterocyclic ring systems having pyrazole, thiophene, thiazole and thiadiazole moieties are synthesised utilising the reaction of sulfur functionalised substrates with α-halocarbonyl compounds and hydrazonyl chlorides.

Synthesis of Some New Indolizine and Pyrrolo[1,2-a]quinoline Derivatives via Nitrogen Ylides

Pyridine and quinoline react with 3-bromoacetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile (2) in dry benzene to give the corresponding pyridinium and quinolinium salts 3 and 9. The latter salts undergo [3+2] 1,3-dipolar cycloaddition with some acetylene and ethylene derivatives to give the corresponding indolizine and pyrrolo[1,2-a]quinoline derivatives Graphical Abstract Synthesis of Some New Indolizine and Pyrrolo[1,2-a]quinoline Derivatives via Nitrogen Ylides

Synthesis of bipyrazole and 1,3,4-thiadiazole derivatives

New hydrazonoyl bromides reacted with several C-nucleophiles to give the corresponding bipyrazoles. Treatment of 3-cyanoacetylpyrazole derivatives with phenyl isothiocyanate in potassium hydroxide followed by hydrazonoyl bromides gave the corresponding pyrazolyl-1,3,4-thiadiazoles.

Facile Synthesis of Thiophene- and 1,3,4-Thiadiazole-Based Heterocycles

Treatment of 3-cyanoacetylpyrazole derivative 1 with phenyl isothiocyanate in potassium hydroxide at room temperature followed by α-haloketones 4a–d and hydrazonoyl halides 10a–e gave the corresponding pyrazolylthiophene 6a–d and pyrazolyl-1,3,4-thiadiazole 12a–e derivatives, respectively.

Genotyping and antimicrobial resistance patterns of Helicobacter pylori in human and dogs associated with A2142G and A2143G point mutations in clarithromycin resistance

BACKGROUND Routes of transmission of Helicobacter pylori a class I carcinogen bacterium and the roles of animals have not been yet well determined. This study was carried out to investigate H. pylori phenotypically and genotypically in human and dogs to determine the antibiotic resistance patterns. As eradication therapy depends mainly on clarithromycin we evaluated 23S rRNA gene mutations associated with its resistance. RESULTS A total of 150 human stool samples and 60 canine gastric biopsies were examined by nested PCR for the presence of H. pylori, 60% and 76.6% were positive respectively. Only 20 (22.2%) and 41 (89.1%) isolates were successfully cultured from human and canine samples respectively. Genotyping revealed a total of cagA+vacA+ combinations 76.6% (69/90) and 65.2% (30/46) in human and dogs, respectively. Allelic diversity in vacA gene was obviously observed, while cagA-vacA+ combinations were 23.3% (21/90) and 34.7% (16/46) in human and dogs, respectively. The antimicrobial susceptibility patterns of human exhibited the highest levels of resistance against Clarithromycin (60%), Trimethoprim (55%), metronidazole (45%), amoxicillin (45%) and cefsulodin (60%) antibiotics and comparatively lower for spiramycin (10%) and tetracycline (15%). Dogs strains showed the highest levels of resistance against Clarithromycin (53.6%), metronidazole (51.2%) and erythromycin (43.9%) antibiotics, on the other hand, the percent of resistant canine strains were comparatively lower for spiramycin (9.7%). Single point mutation of A2143G was detected as 25% (3/12), 18.1% (4/22) in human and dogs respectively. Single point mutation of A2142G was detected as 16.6% (2/12), 13.6% (3/22) in human and dogs, respectively. While dual mutations of both A2142G and A2143G were detected as 50% (6/12), 40.9% (9/22) in human and dogs, respectively. CONCLUSION occurrence of elevated rates of A2142G and A2143G point mutations in clarithromycin resistant H. pylori isolates from human and dogs causing failure in treatment and eradication of the pathogen. The roles of animals need attention and further investigations.