Novel heterocyclic hybrid of 2-(aryl)-1H-indene-1,3(2H)-dione targeting tyrosinase: design, biological evaluation and in silico studies

Document Type : Original Article


1 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, 71348 Shiraz, Iran Central Research Laboratory, Shiraz University of Medical Sciences, 71468 Shiraz, Iran

2 b Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, 71345 Shiraz, Iran

3 Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, 71345 Shiraz, Iran

4 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, 71348 Shiraz, Iran

5 a Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, 71348 Shiraz, Iran

6 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, 71348 Shiraz, Iran Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, 71345 Shiraz, Iran


Melanogenesis is a process of melanin synthesize, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a rate-limiting step of the melanin formation, natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti-tyrosinase agents. Therefore its inhibition may be an efficient way for the development of depigmenting agents. A novel series of 2-arylidine-1H-indene-1,3(2H)-dione analogs were designed, synthesized and screened for their in vitro tyrosinase inhibitory activity. 3d derivative bearing nitrothiophene revealed excellent anti-tyrosinase activity with an IC50 value of 3.55 μM comparable to kojic acid as a positive control. 3d as the most potent inhibitor and 3f as the least active derivative were subjected to in silico evaluations considering the 3D conformations, ΔGb of bindings and interactions within the active site of tyrosinase. 


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