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Synthesis and Pharmacological Evaluation of Novel 1-(2-(Benzoyl-Substituted-2-phenyl-1H-Indol-5-Carbony) Hydrazinyloxy) Vinyl Nitrate Derivatives as Potent Non-Ulcerogenic, Analgesic and Anti-Inflammatory Agents

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Six derivatives of 1-(2-(benzoyl-(substituted)-2-phenyl-1H-indole-5-carbony) hydrazinyloxy) vinyl nitrate were synthesized and tested in vivo for anti-inflammatory, analgesic, and ulcerogenic properties. Synthesized compounds shown significant anti-inflammatory activity comparable to that of Diclofenac sodium in the carrageenan-induced rat paw edema test and all of the compounds were found to be equipotent to Diclofenac sodium in the acetic acid induced writhing analgesic model. Out of six derivatives two derivatives found to produce no ulceration in stomach specimen of rats; nitric oxide seems to contribute to their excellent safety profile which supports several endogenous GIT defense mechanisms, including increase in mucus, bicarbonate secretions, increase in mucosal blood flow, and inhibition of the activation of pro-inflammatory cells by which NO-Indomethacin protects GI mucosa.

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Keywords: 1-(2-(Benzoyl-Substituted-2-phenyl-1H-Indol-5-Carbony) Hydrazinyloxy) Vinyl Nitrate Derivatives; 5-Lipoxygenase; Aspirin; COX-2 inhibitors; Diclofenac; Diclofenac sodium; Dunnet's test; Floctafenine; GIT defense mechanisms; Glafenine; Griess reagent; Haema-toxylin and Eosin staining; Ibuprofen; Indomethacin; Institutional Animal Ethical Committee; Micro analytical Unit; NO-Indomethacin; NO-donor; NSAIDs; Naproxen; National Center for Cell Science; Nitro-Ketoprofen; Nitro-aspirin; Nitro-ibuprofen; Nitro-naproxen; Non-steroidal anti-inflammatory drugs; Rofecoxib; Vasorelaxing Activity; analgesic; anti-inflammatory; bicarbonate secretions; carrageenan-induced rat paw edema method; cy-clooxygenase enzymes; cyclooxy-genase-2; di-methylsulfoxide; edema test; furoxans; hydrazides; infrared spectrometer; mucosal ulceration; nitric oxide; non-ulcerogenic; oximes; plethysmometer; pro-inflammatory cells; prostaglandin biosynthesis; sodium carboxy methyl cellulose; thionyl chloride; titrimetric assays; ulcerogenic properties

Document Type: Research Article

Publication date: 01 July 2010

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