Recently neuroprotective properties of curcumin (Chin 2013) and its synthetically derived pyrazoles and isoxazoles were elucidated by Narlawar et al. 2008. Inhibitory effects of turmeric extracts and curcumin on proliferation and differentiation of human colon cancer cells were presented from our laboratory (ACS 2014). Further green synthesis of curcumin- pyrazole derivative has also been achieved (abstract AGFD ACS 2014). Since curcumin binds to the alpha-helical intermediate and amyloid form of prion protein-inhibiting PrPSc accumulation (J. Neurochem 2008) we required a facile high yielding microwave-induced synthesis of curcumin –pyrazole derivatives. Briefly, curcumin (6mg) was dissolved in ethanol, vortexed and centrifuged. The clear solution (600 µl) was treated with hydrazine monohydrate (300 µl), triethylamine (200 µl), a catalytic amount of glacial acetic acid (100 µl) followed by heating in the domestic microwave oven for 45-50 seconds at 4-second intervals. These reactions have been achieved before at room temperature in 8 hours or under reflux conditions. The reaction mixture was resolved and analyzed by analytical and preparatory TLC (Rf=0.24, CHCl3:CH3OH, 16:4 v/v) and the structure determined via UV-vis, Nano drop and mass spectrometry. LC-MS/MS revealed a molecular ion peak at M/Z=365.2 [M+H]+(ES-API +ve ion mode) confirming the presence of curcumin-pyrazole derivative. We did not have much success with the reagents hydrazine hydrate in THFor hydrazine dihydrochloride in getting the required results. We believe this research has the potential to inhibit amyloid precursor protein (APP) metabolism in Alzheimer’s disease and encapsulation of such curcumin-pyrazoles with Fe3O4-glutathione coated nanoparticles will be helpful in drug delivery Nano therapeutics as well. Molecular docking experiments of hydrazinocurcumin with (Aβ-42, PDB) will reveal if it docks into the hydrophilic pocket of (Aβ-42) in Alzheimer’s disease.

Microwave-induced target orientd synthesis of curcumin-pyrazole derivatives: Potentially important for neuroprotective properties in Alzheimer's disease

253rd National Meeting (2017)

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