ABSTRACT
Fluorescent quinazolinones were synthesized form ethyl 2-methyl-4-oxo-3,4-dihydroquinazoline -5-carboxylate intermediate. The photophysical properties of the compounds were evaluated in DMF solvent. The experimental absorption and emission of the compounds were compared with the vertical excitation and emission obtained Density Functional Theory (DFT) and Time Dependent Density Functional Theory (TD-DFT) computation. Application of the fluorescent compounds as a fluorescent brightening agent was tested on polyester fiber. Changes in the electronic transition, energy levels, and orbital diagrams of quinazolin-4(3H)-one analogues were investigated using the DFT computations and were correlated with the experimental spectral data. The experimental absorption and emission wavelengths are in good agreement with those predicted using the DFT and TD-DFT.
Subject(s)
Bleaching Agents/chemical synthesis , Bleaching Agents/radiation effects , Fluorescent Dyes/chemistry , Quinazolinones/chemistry , Bleaching Agents/chemistry , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/radiation effects , Molecular Structure , Photochemical Processes , Quantum Theory , Quinazolinones/chemical synthesisABSTRACT
BACKGROUND: Tyrosinase inhibitors have become increasingly important because of their ability to inhibit the synthesis of the pigment melanin. A search for new agents with strong tyrosinase activity led to the synthesis of the tyrosinase inhibitor (E)-3-(2,4-dihydroxybenzylidene)pyrrolidine-2,5-dione (3-DBP). METHODS: The inhibitory effect of 3-DBP on tyrosinase activity and melanin production was examined in murine melanoma B16F10 cells. Additional experiments were performed using HRM2 hairless mice to demonstrate the effects of 3-DBP in vivo. RESULTS: The novel compound, 3-DBP, showed an inhibitory effect against mushroom tyrosinase (IC50=0.53 µM), which indicated that it was more potent than the well-known tyrosinase inhibitor kojic acid (IC50=8.2 µM). When tested in B16F10 melanoma cells treated with α-melanocyte stimulating hormone (α-MSH), 3-DBP also inhibited murine tyrosinase activity, which in turn induced a decrease in melanin production in these cells. The anti-melanogenic effect of 3-DBP was further verified in HRM2 hairless mice. The skin-whitening index (L value) of HRM2 hairless mice treated with 3-DBP before irradiation with UVB was greater than that of UVB-irradiated mice that were not treated with 3-DBP. GENERAL SIGNIFICANCE: The newly synthesized 3-DBP has a potent inhibitory effect on tyrosinase. In addition to an in vitro investigation of the effects of 3-DBP on tyrosinase, in vivo studies using an HRM2 hairless mouse model demonstrated the anti-melanogenic potency of 3-DBP. Our newly synthesized 3-DBP showed efficient tyrosinase inhibitory effect in vivo and in vitro. Our finding suggests that 3-DBP can be an effective skin-whitening agent.
Subject(s)
Benzylidene Compounds/chemical synthesis , Benzylidene Compounds/pharmacology , Bleaching Agents/chemical synthesis , Bleaching Agents/pharmacology , Enzyme Inhibitors/pharmacology , Melanins/metabolism , Melanoma, Experimental/drug therapy , Monophenol Monooxygenase/antagonists & inhibitors , Succinimides/chemical synthesis , Succinimides/pharmacology , Agaricales/enzymology , Animals , Blotting, Western , Cell Line, Tumor , Cell Survival/drug effects , In Vitro Techniques , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice , Mice, Hairless , Monophenol Monooxygenase/metabolism , Skin Pigmentation/drug effectsABSTRACT
In order to develop potent skin whitening agents, we have synthesized 17 hydroxyphenyl benzyl ether compounds and tested their melanin synthesis inhibitory activity, DPPH free radical scavenging activity and tyrosinase inhibitory activity. Compounds 32, 35 and 36 possessing 4-hydroxyphenyl benzyl ether structure showed excellent inhibitory capacity with almost 50-fold than arbutin used as a reference in the inhibition test of α-MSH stimulated melanin synthesis in B-16 cells. 4-Hydroxyphenyl benzyl ether compounds also showed good antioxidant activity in the DPPH free radical scavenging test. The tyrosinase function was effectively inhibited by 3,5-dihydroxyphenyl benzyl ether analogues, especially compounds 18, 22, and 24.
