Frontiers in Chemistry (Jun 2022)

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

  • Ya-Guang Hu,
  • Zhu-Peng Gao,
  • Ying-Ying Zheng,
  • Chun-Mei Hu,
  • Jing Lin,
  • Xiao-Zheng Wu,
  • Xin Zhang,
  • Yong-Sheng Zhou,
  • Zhuang Xiong,
  • Dao-Yong Zhu

DOI
https://doi.org/10.3389/fchem.2022.914944
Journal volume & issue
Vol. 10

Abstract

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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 IC50 values of 0.97 μM, which is ∼30 times stronger than the reference inhibitor kojic acid (IC50: 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.

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