Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present article, we have synthesized a combinatorial library of 3,5-diaryl pyrazole derivatives using 8-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-5,7-dimethoxy-2-phenyl-4H-chromen-4-one (1) and hydrazine hydrate in absolute ethyl alcohol under the refluxed conditions. The structures of the compounds were established by IR, (1)H NMR and mass spectral analysis. All the synthesized compounds were evaluated for their anticancer activity against five cell lines (breast cancer cell line, prostate cancer cell line, promyelocytic leukemia cell line, lung cancer cell line, colon cancer cell line) and anti-inflammatory activity against TNF-alpha and IL-6. Out of 15 compounds screened, 2a and 2d exhibited promising anticancer activity (61-73% at 10 microM concentration) against all selected cell lines and IL-6 inhibition (47% and 42% at 10 microM concentration) as in comparison to standard flavopiridol (72-87% inhibition at 0.5 microM) and dexamethasone (85% inhibition at 1 microM concentration), respectively. Cytotoxicity of the compounds checked using CCK-8 cell lines and found to be nontoxic to slightly toxic. Out of 15, four 3,5-diaryl pyrazole derivatives exhibiting potent inhibitory activities against both the monophenolase and diphenolase actions of tyrosinase. The IC(50) values of compounds (2a, 2d, 2h and 2l) for monophenolase inhibition were determined to range between 1.5 and 30 microM. Compounds 2a, 2d, 2h and 2l also inhibited diphenolase significantly with IC(50) values of 29.4, 21.5, 2.84 and 19.6 microM, respectively. All four 3,5-diaryl pyrazole derivatives were active as tyrosinase inhibitors (2a, 2d, 2h and 2l), and belonging to competitive inhibitors. Interestingly, they all manifested simple reversible slow-binding inhibition against diphenolase.
 ...
PMID:Synthesis of novel 3,5-diaryl pyrazole derivatives using combinatorial chemistry as inhibitors of tyrosinase as well as potent anticancer, anti-inflammatory agents. 2063 87

Both high-intensity ultraviolet and narrowband ultraviolet B (NB-UVB) are important therapeutic options for vitiligo management, but high-intensity ultraviolet is more effective than NB-UVB. However, the underlying mechanisms have not been well investigated. Herein, we compare the effects of high-intensity ultraviolet and NB-UVB on the pigmentation of melanocytes derived from hair follicle-derived neural crest stem cells (HF-NCSCs) in vitro and study the underlying mechanisms. The HF-NCSCs were isolated from mouse whisker follicles. After radiation with high-intensity ultraviolet and NB-UVB, respectively, the cell viability by the CCK-8 assay showed gradual inhibitory effects in a dose-dependent manner, which has no apparent difference between the two modalities. The mRNA for melanogenesis factors such as tyrosinase and tyrp1 of the differentiated melanocytes increased significantly with high-intensity ultraviolet compared to the same dose of NB-UVB exposure. Furthermore, the expression of Mc1r was significantly increased by high-intensity ultraviolet in contrast to NB-UVB at the dosage of 0.5 J. By and large, these data suggest that high-intensity ultraviolet exhibited greater efficiency on the maturation of the melanocyte lineage differentiated from HF-NCSCs compared to NB-UVB with the same dose, which was probably due to the stronger stimulatory action of Mc1r. This may provide new insights into the different efficacies of high-intensity ultraviolet and NB-UVB in the treatment of vitiligo repigmentation.
 ...
PMID:Comparison of high-intensity ultraviolet and NB-UVB on the maturation of melanocytes derived from hair follicle neural crest stem cells. 2471 Oct 10