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

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.

Synthesis, characterization and in vitro antimicrobial activity of novel 2-thioxo-4-thiazolidinones and 4,4'-bis(2-thioxo-4-thiazolidinone-3-yl)diphenylsulfones.

2-Thioxo-4-thiazolidinones (3a,b) were achieved by cyclocondensation of isothiocyanatosulfonamides (1a,b) with sulfanylacetic acid at reflux temperature in dioxane in the presence of triethylamine. Compound (3a) was exploited to synthesize the versatile hitherto unknown 2-thioxo-4-thiazolidinones (5-10) via its reaction with some electrophiles. Cyclization of 4,4'-diisothiocyanate diphenylsulfone (11) with sulfanylacetic acid furnished 4,4'-bis(2-thioxo-4-thiazolidinone-3-yl)diphenylsulfone (12) which on treatment with excess 4-methoxybenzaldehyde in refluxing dioxane in the presence of piperidine yielded the bisbenzylidene derivative (13). The novel synthesized compounds were characterized by IR, (1)H NMR and mass spectral studies. All the synthesized compounds were screened in vitro for their antibacterial and antifungal activities.