2. Academic Validation
  3. Discovery, total synthesis, and biological evaluation of tyrcinnamins as antibacterial agents and tyrosinase activators

Discovery, total synthesis, and biological evaluation of tyrcinnamins as antibacterial agents and tyrosinase activators

  • Eur J Med Chem. 2025 Jul 5:291:117665. doi: 10.1016/j.ejmech.2025.117665.
Di Mao 1,  Baoyue Wei 2,  Chao Liu 3,  Bing Zhang 4,  Zhiwei Zhang 5,  Yuhan Zhang 2,  Zhuang Li 2,  Boxiang Ding 4,  Hai Ye 4,  Jingjing Wang 6,  Lijuan Sun 6,  Yanan Gai 5,  Pengwei Yu 2,  Hideaki Kakeya 7,  Shan Lu 8
Affiliations

Affiliations

  • 1 School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China; Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
  • 2 School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China.
  • 3 College of Biological and Food Engineering, Hubei Minzu University, Enshi, 445000, Hubei Province, PR China.
  • 4 Nanjing Heron Pharmaceutical Science and Technology Co., Ltd., Nanjing, 211112, PR China.
  • 5 Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, 210014, PR China.
  • 6 College of Pastoral Agricultural Science and Technology, Lanzhou University, West Jiayuguan Road 768, Lanzhou, 730020, PR China.
  • 7 Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
  • 8 School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China. Electronic address: lushan@ujs.edu.cn.
PMID: 40286627 DOI: 10.1016/j.ejmech.2025.117665
Abstract

Microorganisms serve as critical resources for the discovery of new Antibacterial drug leads. Herein, we report the screening, isolation, and identification of tyrcinnamin (1) from the endophytic Streptomyces sp. JS-B1. The total synthesis, biological evaluation, and structural-activity relationship study of tyrcinnamin and its synthetic derivatives led to the discovery of 7a, a promising lead compound with significant Antibacterial activity, notable Tyrosinase activation activity, and an excellent safety profile. The analysis of molecular docking of 7a with mushroom Tyrosinase reveals that 7a may competitively occupy the binding site of l-DOPA on the surface of Tyrosinase without interfering with the substrate binding at the active center, thereby reducing the ineffective occupancy of l-DOPA on the Tyrosinase surface and improving the binding efficiency of l-DOPA at the active center. The structure of 7a represents a new chemical scaffold for the development of new Antibiotics and Tyrosinase activators, making valuable contributions to both drug discovery and cosmetics development.

Keywords

Antibacterial activity; Natural product; Total synthesis; Tyrosinase activation.

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