Facile synthesis of substituted indazolo-phthalazine-trione compounds with antibacterial, antioxidant, anti-inflammatory and antidiabetic activity

Abstract

A new synthetic route for preparation of 2H-Indazolo[2,1-b]phthalazine-1,6,11(13H)-trione is reported by one pot three component condensation reaction of phthalhydrazide, aromatic aldehydes and dimedone with Eaton's reagent under solvent free conditions at room temperature in good to excellent yields. Easy workup, no column chromatography, short reaction time are some of the highlights of this protocol. Five new compounds are prepared in this study. All the prepared compounds were assessed for their biological activities, wherein Indazolo-phthalazine-trione compound 1a with p-methyl substituent was highly efficient in inhibiting bacterial test pathogens with MIC values between 0.25-0.5 MU g/mL followed by compound 1d with o-chloro substituent with MIC values between 0.5 and 1.0 Mu g/mL. Both these compounds 1a and 1d also exhibited DPPH-free radical scavenging activity with IC sub(50) values 52.89 plus-minus 0.56 and 54.04 plus-minus 0.58 Mu g/mL respectively, indicating their high antioxidant potency. These compounds were also highly effective in anti-inflammatory activity, with IC sub(50) values of 47.67 plus-minus 0.84 and 48.52 plus-minus 0.99 Mu g/mL for 1a and 1d respectively. Further, compound 1o with o-fluoro substituent was the most potent in inhibiting alpha-amylase and alpha-glucosidase activity with IC sub(50) values 32.30 plus-minus 1.04 and 14.56 plus-minus 0.29 Mu g/mL, followed by 1q with o, p-dimethyl substituents exhibiting IC sub(50) values 38.43 plus-minus 1.07 and 19.34 plus-minus 0.55 Mu g/mL respectively and were considered excellent antidiabetic compounds.