Synthesis, characterization, and antioxidant and bleomycin-dependent DNA damage evaluation of curcumin analogs

Abstract

In an attempt to find a new class of antioxidant agents, a series of pyrazole, pyridopyrazoltriazine, pyrazolotriazine, isoxazole, and pyridine-containing products were prepared, starting with curcumin and appropriate chemical reagents. Thus, curcumin 1 undergoes coupling reaction with diazonium salts 2-5 to afford the corresponding 4-arylazo derivatives 6-9. Heating of 6 and/or 7 in acetic acid furnished the corresponding pyrazolotriazines 10 and 11. Also, pyrazole and isoxazole derivatives were obtained upon treatment of 10 with hydrazines or hydroxylamine hydrochloride. Furthermore, multicomponent reaction of 10 with malononitrile/CH3 COONH4 or phenacylpyridinium iodide/CH3 COONH4 produced the corresponding bispyridines 16 and 17, respectively. Furthermore, condensation of 10 with guanidine nitrate or thiourea gave the corresponding pyrimidines 18 and 19, respectively. Finally, other curcumin derivatives were obtained on condensation of 1 with isatins and pyrazole-4-aldehyde. The newly synthesized compounds were evaluated as antioxidant agents. The results showed clearly that most of the compounds exhibited good activities, except for compounds 9 and 12. Compounds 1, 3, 15, and 23 exhibited high protection against DNA damage induced by the bleomycine-iron complex.

Keywords: Antioxidant activity; Curcumin; Indole; Oxazole; Pyrazole; Pyrimidine.