Rational Design and Synthesis of 4-O-Substituted Phenylmethylenethiosemicarbazones as Novel Tyrosinase Inhibitors

Abstract

In continuing our program aimed to search for tyrosinase inhibitors, a series of novel 4-O-substituted phenylmethylenethiosemicarbazones were rational designed, synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were also evaluated. A fair number of compounds were found to have significant tyrosinase inhibitiory activity. Particularly, the IC 50 values of compounds 3a-g, 3j and 3s were of the same magnitude as tropolone, one of the best tyrosinase inhibitors known so far. Furthermore, the structure-activity relationships of these compounds were also investigated. All these data suggested that these molecules might be utilized for the development of new candidate for the treatment of dermatological disorders, and further development of such compounds may be of interest.Key words synthesis; tyrosinase inhibitory activity; the structure-activity relationship; 4-O-substituted phenylmethylenethiosemicarbazone Chem. Pharm. Bull. 58(5) 752-754 (2010)

Study on Synthesis and Biological Evaluation of 3-Aryl Substituted Xanthone Derivatives as Novel and Potent Tyrosinase Inhibitors

“…Chemistry The 1 H-NMR and 13 C-NMR spectra were recorded using tetramethylsilane (TMS) as the internal standard on a Bruker Avnace III 400 spectrometer or JOEL ECA-400 spectrometers at 400 MHz and 101 MHz in either CDCl 3 , DMSO-d 6 or Acetone-d 6 . Chemical shifts (δ) were referenced to TMS as an internal standard ( 1 H-NMR, 13 C-NMR). Coupling constants are given in Hz.…”

“…12) Moreover, excessive accumulation of melanin in the mammalian brain caused by abnormal tyrosinase activity is linked to the neurodegenerative diseases including Parkinson's disease. 13) Obviously, the unregulated action of tyrosinase has become an important factor in a number of human disease etiologies. Accordingly, tyrosinase inhibitors have been ardently explored as an avenue for therapies to these diseases and have become increasingly important in agriculture and food industry, as well as in medicinal and cosmetic products.…”

Natural and Synthetic Tyrosinase Inhibitors as Antibrowning Agents: An Update

“…In continuing searching of novel tyrosinase inhibitors Yi and others (2010a) synthesized and tested a series of 4‐ O ‐substituted phenylmethylenethiosemicarbazones. The (1‐(1‐(4‐(2‐(2‐methoxyethoxyl)ethoxyl))benzyliene)thiosemicarbazide) ( 48 ) exhibited a strong inhibitory activity with an IC 50 value of 0.34 μM.…”

Design, Synthesis, Biological Evaluation and Inhibition Mechanism of 3-/4-Alkoxy Phenylethylidenethiosemicarbazides as New, Potent and Safe Tyrosinase Inhibitors

“…The inhibition of target compounds on the diphenolase activity of mushroom tyrosinase was investigated by the reported procedure [45][46][47][48][49][50][51][52][53] with some slight modifications. Briefly, all the synthesized compounds were screened for the diphenolase inhibitory activity of tyrosinase using L-DOPA as substrate.…”