Newly synthesized piperazine derivatives as tyrosinase inhibitors: in vitro and in silico studies

• Published in: Journal of the Iranian Chemical Society 2022-07, Vol.19 (7), p.2739-2748
• Main Authors: Dokuzparmak, Cigdem, Oz Tuncay, Fulya, Basoglu Ozdemir, Serap, Kurnaz, Busra, Demir, Ilke, Colak, Ahmet, Sag Erdem, Safiye, Yildirim, Nuri
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Biochemistry; Chemistry; Chemistry and Materials Science; Inhibitors; Inorganic Chemistry; Molecular docking; Organic Chemistry; Organic compounds; Original Paper; Physical Chemistry; Synthesis; Tyrosinase
• ISSN: 1735-207X; 1735-2428
• DOI: 10.1007/s13738-021-02487-3

In this study, a series of new organic compounds with piperazine as a fundamental skeleton was synthesized and evaluated for their tyrosinase inhibitory potentials by in vitro and in silico studies. The in vitro studies have shown that compounds 10a and 10b bearing 1,2,4, triazole nucleus could be considered potent tyrosinase inhibitors with IC 50 values of 31.2 ± 0.7 and 30.7 ± 0.2 µM, respectively. 10b (K i  = 9.54 µM, mixed type inhibition) with the lowest IC 50 value among derivatives was selected to determine kinetic constants and inhibition types. Furthermore, molecular docking analysis was performed for all compounds and it was observed that 4b, 5a, 4c, and 10b showed promising inhibitory effect on tyrosinase activity. Based on docking results, ADME predictions and in vitro studies, 10b might be considered suitable oral drug candidates for further studies.