mannich-bases and 1-3-4-oxadiazole

A series of novel ibuprofen and salicylic acid-based 3,5-disubstituted-1,3,4-oxadiazole-2(3H)-thione derivatives was synthesized, and they were evaluated as potential anti-inflammatory agents. Following the structure identification studies employing IR,

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Cell Survival; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Dinoprostone; Dose-Response Relationship, Drug; Humans; Lipopolysaccharides; Mannich Bases; Molecular Docking Simulation; Molecular Structure; Nitric Oxide; Oxadiazoles; Structure-Activity Relationship; Thiones

The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in treatment of different chronic inflammatory disorders is strongly restricted by their serious gastrointestinal adverse effects. Therefore, there is still an urgent need to search for new, safe, and efficient anti-inflammatory agents. Previously, we have reported the Mannich base-type derivatives of pyrrolo[3,4-

Topics: Antioxidants; Catalytic Domain; Cell Line; Cell Survival; Circular Dichroism; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Drug Design; Female; Fibroblasts; Humans; Inhibitory Concentration 50; Mannich Bases; Middle Aged; Molecular Docking Simulation; Molecular Structure; Oxadiazoles; Pyridazines; Pyrroles; Serum Albumin, Bovine; Structure-Activity Relationship

A series of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases have been conveniently synthesized in good yields. Their structures were characterized by IR, (1)H NMR, (13)C NMR and elemental analysis. The preliminary bioassay results indicated that some of the compounds showed promising in vitro fungicidal activities towards several test plant fungi; some of them exhibited significant herbicidal activities against Brassica campestris and excellent in vitro inhibitory activities against rice ketol-acid reductoisomerase (KARI). Among 14 novel compounds, 8c, 8d and 8m showed potent KARI inhibitory activities with Ki value of (0.96±0.42), (3.86±0.49) and (3.10±0.71) μmol/L, respectively, and were comparable with IpOHA. These compounds could be novel KARI inhibitors for further investigation. The density functional theory (DFT) calculations and molecular docking were carried out to study the structure-activity relationship (SAR) of the active inhibitors in this Letter.

Topics: Carbon-13 Magnetic Resonance Spectroscopy; Enzyme Inhibitors; Ketol-Acid Reductoisomerase; Mannich Bases; Molecular Structure; Oxadiazoles; Proton Magnetic Resonance Spectroscopy; Spectrophotometry, Infrared; Structure-Activity Relationship