N-Phenylthiourea is a phenoloxidase inhibitor. N-Phenylthiourea inhibits the enzymatic oxidation of dopamine by phenoloxidase (Ki=0.21μM). N-Phenylthiourea reduces melanin synthesis to improve imaging transparency in zebrafish embryos. N-Phenylthiourea is used for taste genetics and antimicrobial activity evaluation[1-4].
In vitro, treatment with 10μM-1mM N-Phenylthiourea for 5 days decolorized SKMEL-188 cells and decreased tyrosinase activity[5]. Treatment with 0.5mM N-Phenylthiourea for 1-7 days caused intercellular space formation, perinuclear aggregation of pigment granules, rounding, blebbing, and lysis in CuCl2-induced KB, B-16, and N-115 cells[6]. Treatment with 1mM N-Phenylthiourea for 72 hours reduced melanin content and decreased DOPA oxidase activity of TYR in MNT-1 cells[7].
In vivo, administration of 25-55mg/kg/day N-Phenylthiourea in drinking water to black rats for 130-152 days inhibited skin melanin production, turned regenerating fur cream-colored or brown, caused pepper-and-salt greying, and led to pigment return within 8 days and glossy black fur regrowth within 21 days after withdrawal[8]. Administration of 60-120mg/kg N-Phenylthiourea in feed to Fischer 344 rats for 78 weeks did not induce chemically related tumors and caused no abnormal clinical signs. Administration of 150-300mg/kg N-Phenylthiourea in feed to B6C3F1 mice for 78 weeks suppressed body weight gain and did not induce chemically related tumors[9].
References:[1] Ha YM, Park YJ, Lee JY, et al. Design, synthesis and biological evaluation of 2-(substituted phenyl)thiazolidine-4-carboxylic acid derivatives as novel tyrosinase inhibitors. Biochimie. 2012 Feb;94(2):533-40.
[2] Ha YM, Park YJ, Kim JA, et al. Design and synthesis of 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives as novel tyrosinase inhibitors. Eur J Med Chem. 2012 Mar;49:245-52.
[3] Park KL. Emergence of hydrogen bonds from molecular dynamics simulation of substituted N-phenylthiourea-catechol oxidase complex. Arch Pharm Res. 2017 Jan;40(1):57-68.
[4] Huong DQ, Duong T, Nam PC. Experimental and theoretical study of corrosion inhibition performance of N-phenylthiourea for mild steel in hydrochloric acid and sodium chloride solution. J Mol Model. 2019 Jun 27;25(7):204.
[5] Slominski A, Zbytek B, Slominski R. Inhibitors of melanogenesis increase toxicity of cyclophosphamide and lymphocytes against melanoma cells. Int J Cancer. 2009 Mar 15;124(6):1470-7.
[6] Masuda A, Eguchi G, et al. Phenylthiourea enhances Cu cytotoxicity in cell cultures: its mode of action. Cell Struct Funct. 1984;9(1):25-35.
[7] Kleszczynski K, Kim T-K, Bilska B, et al. Melatonin exerts oncostatic capacity and decreases melanogenesis in human MNT-1 melanoma cells. J Pineal Res. 2019 Nov;67(4):e12610.
[8] Dieke S, Richter C, Clisby K, et al. Pigmentation and hair growth in black rats, as modified by the chronic administration of thiourea, phenyl thiourea and alpha-naphthyl thiourea. Endocrinology. 1947 Mar;40(3):123-35.
[9] National Cancer Institute. Bioassay of 1-phenyl-2-thiourea for possible carcinogenicity. Natl Cancer Inst Carcinog Tech Rep Ser. 1978;(148):1-40.