Synthesis and biological evaluation of kojic acid derivatives containing 1,2,4-triazole as potent tyrosinase inhibitors.
A series of 5-substituted-3-[5-hydroxy-4-pyrone-2-yl-methymercapto]-4-amino-1,2,4-triazole derivatives were synthesized by nucleophilic substitution reaction of 5-hydroxy-2-chloromethyl -4H-pyran-4-one with 5-substituted-3-mercapto-4-amino-1,2,4-triazole, and their inhibitory effects on mushroom tyrosinase were evaluated. The results indicated that most of the synthesized compounds exhibited significant inhibitory activity. Specifically, 5-(4-chlorophenyl)-3-[5-hydroxy-4-pyrone-2-yl-methymercapto]-4-amino-1,2,4-triazole (6j) exhibited the most potent tyrosinase inhibitory activity with IC50 value of 4.50 ± 0.34 μm. The kinetic studies of the compound (6j) demonstrated that the inhibitory effects of the compound on the tyrosinase were belonging to competitive inhibitors. Meanwhile, the structure-activity relationship was also discussed.
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.|Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, 411201, China.|Hunan Provincial University Key Laboratory of QSAR/QSPR, Xiangtan, 411201, China.
Wenlin
W
Xie
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.|Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, 411201, China.|Hunan Provincial University Key Laboratory of QSAR/QSPR, Xiangtan, 411201, China.
Jingai
J
Zhang
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.|Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, 411201, China.|Hunan Provincial University Key Laboratory of QSAR/QSPR, Xiangtan, 411201, China.
Xiaojing
X
Ma
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.|Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, 411201, China.|Hunan Provincial University Key Laboratory of QSAR/QSPR, Xiangtan, 411201, China.
Wenqian
W
Yang
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.|Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, 411201, China.|Hunan Provincial University Key Laboratory of QSAR/QSPR, Xiangtan, 411201, China.
Ying
Y
Zhou
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.|Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, 411201, China.|Hunan Provincial University Key Laboratory of QSAR/QSPR, Xiangtan, 411201, China.
Xufu
X
Tang
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.|Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, 411201, China.|Hunan Provincial University Key Laboratory of QSAR/QSPR, Xiangtan, 411201, China.
Yan
Y
Zou
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.|Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, 411201, China.|Hunan Provincial University Key Laboratory of QSAR/QSPR, Xiangtan, 411201, China.
Hui
H
Li
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.|Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, 411201, China.|Hunan Provincial University Key Laboratory of QSAR/QSPR, Xiangtan, 411201, China.
Jingjing
J
He
Hunan University of Humanities, Science and Technology, Loudi, 417000, China.
Shimin
S
Xie
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.|Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, 411201, China.|Hunan Provincial University Key Laboratory of QSAR/QSPR, Xiangtan, 411201, China.
Yunhui
Y
Zhao
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.|Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, 411201, China.|Hunan Provincial University Key Laboratory of QSAR/QSPR, Xiangtan, 411201, China.
Fengping
F
Liu
D000363:Agaricales / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D011753:Pyrones; D014230:Triazoles; C045575:1,2,4-triazole; C011890:kojic acid; D014442:Monophenol Monooxygenase
1,2,4-triazole; kojic acid derivatives; mushroom tyrosinase; tyrosinase inhibitors