Synthesis and antityrosinase, antioxidant activities of phloretin thiosemicarbazones

Three phloretin derivates were achieved through condensation of the phloretin template with thiosemicarbazide, 4-methylthiosemicarbazide, and 4-phenyl-3-thiosemicarbazide. Their purity was confirmed by high-performance liquid chromatograph and their structures were determined from their ultraviolet spectra, Fourier-transform infrared, H-1 and C-13 NMR, and mass spectra. The solubility of these novel compounds in ultrapure water at 25 A degrees C was significantly improved compared with that of phloretin in the following order: phloretin thiosemicarbazone (PT, > 1.00 mg/mL) > phloretin-4-phenyl-3-thiosemicarbazone (PPT, 0.52 mg/mL) > phloretin-4-methylthiosemicarbazone (PMT, 0.24 mg/mL) > phloretin (0.02 mg/mL). The tyrosinase inhibitory effect and various antioxidant assays in vitro were evaluated. Results showed that PT possesses potent tyrosinase inhibitory activity (IC50 = 57.81 +/- A 1.46 mu M), which was better than phloretin (IC50 = 70.08 +/- A 0.88 mu M). They also significantly quenched 1,1-diphenyl-2-picryl-hydrazyl and exhibited strong activity against the lipid peroxidation induced by Fe2+/ascorbic acid. Likewise, these compounds significantly protected against 2,2'-azo-bis(2-amidinopropane)dihydrochloride-induced Cu, Zn-superoxide dismutase, and pBR322 plasmid DNA damage in a dose-dependent manner.