Synthesis and Evaluation of 2(3H)-Thiazole Thiones as Tyrosinase Inhibitors

• Published in: Archiv der Pharmazie (Weinheim) Vol. 345; no. 8; pp. 629 - 637
• Main Authors: Emami, Saeed, Hosseinimehr, Seyed Jalal, Shahrbandi, Kami, Enayati, Ahmad Ali, Esmaeeli, Zahra
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-08-2012; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: ADME-Tox screening; Drug Evaluation, Preclinical - methods; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; In Vitro Techniques; Inhibitory Concentration 50; Molecular Structure; Monophenol Monooxygenase - antagonists & inhibitors; Phenolic antioxidants; Pyrones - pharmacology; Radical scavenging activity; Structure-Activity Relationship; Thiazole; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Thiazoline; Thiones - chemical synthesis; Thiones - chemistry; Thiones - pharmacology; Tyrosinase inhibitors
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201200028

A series of 2(3H)‐thiazole thiones 3–5 was synthesized and evaluated for tyrosinase inhibition and DPPH radical scavenging activities. Among them, 3‐methyl‐4‐phenyl‐2(3H)‐thiazole thione (4a) showed good tyrosinase inhibitory activity, even better than that of the well‐known tyrosinase inhibitor, namely, kojic acid. From the structure–activity point of view, although it was found that the phenolic hydroxyl group in prototype 3–5 might contribute to the scavenging activity against DPPH radicals, there was no correlation between the potency of tyrosinase inhibition and the presence of the phenolic moiety. The in silico ADME‐Tox screening revealed that the drug‐likeness and drug‐score values of the most potent compound 4a were significantly higher than those of kojic acid.
A series of 2(3H)‐thiazole thiones were synthesized and evaluated for their tyrosinase inhibition and DPPH radical scavenging activities. Among them, 3‐methyl‐4‐phenyl‐2(3H)‐thiazole thione (4a) showed good tyrosinase inhibitory activity.