One‐pot cascade synthesis and in vitro evaluation of anti‐inflammatory and antidiabetic activities of S‐methylphenyl substituted acridine‐1,8‐diones

Various S‐methylphenyl substituted acridine‐1,8‐dione series ( 4a–i ) were synthesized through a one‐pot cascade synthetic approach involving the reaction of 4‐(methylthio)benzaldehyde and dimedone with a variety of amines as nitrogen source under reflux in ethanol. All the synthesized derivatives were characterized by using spectroscopic methods. In vitro evaluations of anti‐inflammatory and antidiabetic efficacies of all the synthesized compounds were investigated. The anti‐inflammatory results infer that the compounds 4c and 4d are showing excellent activity with an inhibition percentage of 80.58 ± 0.42, 81.72 ± 1.72 by membrane stabilization and 77.72 ± 0.76, 78.76 ± 0.81 by albumin denaturation methods, which is comparable with the standard diclofenac at a concentration of 100 μg/ml. Further, the antidiabetic assay revealed the moderate activity for the synthesized compounds at a concentration of 100 μg/ml with respect to their standard drug, acarbose.     

Subchronic toxicity of all-trans-retinoic acid and retinylidene dimedone in Sprague-Dawley rats

Sprague-Dawley rats received daily oral gavage doses of either 2-retinylidene-5,5-dimethyl-1,3-cyclohexanedione (retinylidene dimedone; 14, 50, 150, or 330 mg/kg) or all-trans-retinoic acid (1, 4, 14, or 50 mg/kg) for 13 weeks. Rats given 50 mg/kg of all-trans-retinoic acid developed numerous long-bone fractures and became moribund during the third week of the study. Those receiving lower dosages survived until scheduled termination, but the 14 mg/kg group showed clear signs of retinoid intoxication including growth depression, anemia, serum alkaline phosphatase elevation, bone fracture, and testicular degeneration. Exposure to retinylidene dimedone did not result in any treatment-related deaths, growth depression, or histopathologic lesions, even at the highest dose, 300 mg/kg. Animals given this dosage exhibited mild anemia, equivocal evidence of bone fracture, but no increase in alkaline phosphatase activity. Retinylidene dimedone appears to be considerably less toxic than all-trans-retinoic acid.