Some Novel Mannich Bases of 5‐(3,4‐Dichlorophenyl)‐1,3,4‐oxadiazole‐2(3H)‐one and Their Anti‐Inflammatory Activity

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for the treatment of rheumatic arthritis, pain, and many different types of inflammatory disorders, cause serious gastrointestinal (GI) side effects. The free carboxylic acid group existing on their chemical structure is correlated with GI toxicity related with all routine NSAIDs. Replacing this functional group with the 1,3,4-oxadiazole bioisostere is a generally used strategy to obtain an anti-inflammatory agent devoid of GI side effects. In the present work, a novel group of 5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one Mannich bases were synthesized and characterized on the basis of IR, H NMR, and elemental analysis results. The target compounds were first tested for cytotoxicity to determine a non-toxic concentration for anti-inflammatory screening. Anti-inflammatory effects of the compounds were evaluated by in vitro lipopolysaccharide (LPS)-induced NO production and in vivo carrageenan footpad edema with ulcerogenic profile. In LPS-induced RAW 264.7 macrophages, most of the compounds showed inhibitory activity on nitrite production while compounds 5a, 5h, and 5j exhibited the best profiles by suppressing the NO production. To evaluate the in vivo anti-inflammatory potency of the compounds, the inflammatory response was quantified by increment in paw size in the carrageenan footpad edema assay. The anti-inflammatory data scoring showed that compounds 5a-d, 5g, and 5j, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5g was comparable to that of the reference drug indomethacin with 53.9% and 55.5% inhibition in 60 and 120 min, respectively.

Design, synthesis, and biological evaluation of new pyrazoloquinazoline derivatives as dual COX‐2/5‐LOX inhibitors

“…Male albino rats of Sprague Dawley strain, weighing 130-150 g, [44,45] were kept in the animal house unit of pharmacology and toxicology department for at least 1 week before the experiment under standard conditions of light and temperature. All animals were fed a standard laboratory diet consisting of vitamin mixture (1%), mineral mixture (4%), corn oil (10%), sucrose (20%), cellulose (0.2%), casein 95% pure (10.5%), and starch (54.3%).…”

Synthesis and biological evaluation of pyrazolone analogues as potential anti‐inflammatory agents targeting cyclooxygenases and 5‐lipoxygenase

“…Adult male albino rats of Sprague Dawley strain weighing 130–150 g [ 40,41 ] were kept in the animal house unit of the pharmacology and toxicology department for a least 1 week before the experiments under standard conditions of light and temperature. All animals were accessed to standard laboratory diet consisting of vitamin mixture (1%), mineral mixture (4%), corn oil (10%), sucrose (20%), cellulose (0.2%), casein 95% pure (10.5%), and starch (54.3%).…”

“…Compounds 3f , 3h , 3l , and 3p were evaluated for their in vivo AI activity by applying the carrageenan‐induced rat paw edema screening protocol as an acute inflammation model [ 42 ] according to a previously reported method after oral administration of a dose of 10 mg/kg of tested compounds as well as reference drugs. [ 40,43,44 ] The rats were marked and divided into eight experimental groups of six rats each. The first group received 1 ml saline and served as untreated control.…”

One-Pot Multicomponent Synthesis and Bioevaluation of Tetrahydroquinoline Derivatives as Potential Antioxidants, α-Amylase Enzyme Inhibitors, Anti-Cancerous and Anti-Inflammatory Agents

“…An excess amount of nitric oxide (NO) is associated with several diseases, i.e., inflammation, cancer and other pathological conditions. Therefore, NO production inhibition is a principle key factor for the screening of drugs with anti-inflammatory potential [85].…”

“…The in vivo anti-inflammatory activity was performed following the procedure described by Koksal, et al [85] in 2017. Paw edema was induced by injecting 100 µL of 1% sterile carrageenan solution into the right hind paw of mice.…”