Modulatory effects of new curcumin analogues on gamma-irradiation - Induced nephrotoxicity in rats

- A series of new 2-amino-pyran-3-carbonitrile derivatives of curcumin 2-7 were synthesized.
- These new compounds were evaluated to treat nephrotoxicity induced by γ-irradiation in rats.
- They attenuate the nephrotoxicity by activation of Nrf2 and down-regulation of NF-κB.
- Thus, these compounds improved the antioxidant and anti-inflammatory activities in kidney.
- Chloro-phenyl derivative 7 is the most active one to treat nephrotoxicity induced by γ-radiation.

In the present study, a new series of 2-amino-pyran-3-carbonitrile derivatives of curcumin 2-7 have been synthesized via one-pot simple and efficient protocol, involving the reaction of curcumin 1 with substituted-benzylidene-malononitrile to modify the 1,3-diketone moiety. The structures of the synthesized compounds 2-7 were elucidated by microanalytical and spectral data, which were found consistent with the assigned structures. The nephroprotective mechanism of these new curcumin analogues was evaluated on the post-gamma-irradiation (7 Gy) - induced nephrotoxicity in rats. Activation of Nrf2 by these curcumin analogues is responsible for the amendment of the antioxidant status, impairment of NF-κB signal, thus attenuate the nephrotoxicity induced post-γ-irradiation exposure. 4-Chloro-phenyl curcumin analogue 7 showed the most potent activity. In conclusion, the results of the present study demonstrate a promising role of these new curcumin analogues to attenuate the early symptoms of nephrotoxicity induced by γ-irradiation in rats via activation of Nrf2 gene expression. These new curcumin analogues need further toxicological investigations to assess their therapeutic index.

86