Synthesis and Biological Activity Evaluation of 2-Cyanopyrrole Derivatives as Potential Tyrosinase Inhibitors

• Published in: Frontiers in chemistry 2022-06, Vol.10, p.914944-914944
• Main Authors: Hu, Ya-Guang, Gao, Zhu-Peng, Zheng, Ying-Ying, Hu, Chun-Mei, Lin, Jing, Wu, Xiao-Zheng, Zhang, Xin, Zhou, Yong-Sheng, Xiong, Zhuang, Zhu, Dao-Yong
• Format: Article
• Language: English
• Subjects: 2-cyanopyrrole; Chemistry; mixed-type inhibitor; molecular docking; reversible inhibitor; tyrosinase
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2022.914944

In order to find potential inhibitors of tyrosinase, two series of pyrrole derivatives A (1–17) and B (1–8) were synthesized and screened for their inhibitory activities on tyrosinase. Most of the 2-cyanopyrrole derivatives exhibited effective inhibitory activities. In particular, A12 exhibited the strongest inhibitory activities, with the IC 50 values of 0.97 μM, which is ∼30 times stronger than the reference inhibitor kojic acid (IC 50 : 28.72 μM). The inhibitory mechanism analysis results revealed that A12 was a reversible and mixed-type inhibitor. Molecular docking experiments clarified the interaction between A12 with tyrosinase. Furthermore, A12 (100 μM) presented effective inhibitory effect on tyrosinase in B16 melanoma cells with inhibition of 33.48%, which was equivalent to that of Kojic acid (39.81%). Accordingly, compound A12 may serve as the lead structure for the further design of potent tyrosinase inhibitors. Molecular docking studies confirmed the interaction between the compound and tyrosinase.