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.
Farghaly
Thoraya A
TA
Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt. thoraya-f@hotmail.com
Abdel Hafez
Naglaa A
NA
Ragab
Eman A
EA
Awad
Hanem M
HM
Abdalla
Mohamed M
MM
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000737:chemistry; D001921:Brain / Q000187:drug effects / Q000821:virology; D006224:Cricetinae; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors*; D010851:Picrates / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D012093:Replicon / Q000187:drug effects; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000975:Antioxidants; D000998:Antiviral Agents; D001713:Biphenyl Compounds; D006574:Heterocyclic Compounds, 2-Ring; D030421:Peroxynitrous Acid; D010851:Picrates; D011725:Pyridines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C004931:1,1-diphenyl-2-picrylhydrazyl; C023666:pyridine