2. Academic Validation
  3. Genome-guided discovery of coublibactins from Nocardia coubleae and their gallium complexes with potent antileukemic activity

Genome-guided discovery of coublibactins from Nocardia coubleae and their gallium complexes with potent antileukemic activity

  • Bioorg Chem. 2025 Jun 15:160:108508. doi: 10.1016/j.bioorg.2025.108508.
Qiaoqiao Tao 1,  Teng Cai 2,  Yang Xiao 2,  Tao Han 2,  Ling Shen 2,  Chang Cheng 2,  Shouying Xu 3,  Aiying Li 3,  Peng Zhang 2,  Jiachun Chen 2,  Yonghui Zhang 2,  Qingyi Tong 4,  Xiaofeng Cai 5
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Key Laboratory of Neurological Diseases of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.
  • 2 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Key Laboratory of Neurological Diseases of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
  • 3 State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, PR China.
  • 4 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Key Laboratory of Neurological Diseases of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: qytong@hust.edu.cn.
  • 5 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Key Laboratory of Neurological Diseases of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: caixiaofeng@hust.edu.cn.
PMID: 40280014 DOI: 10.1016/j.bioorg.2025.108508
Abstract

The pursuit of highly effective and selective Anticancer drugs remains a critical challenge. Metal-based complexes, particularly gallium-containing compounds, offer promising therapeutic avenues due to their unique mechanisms of action. To identify novel scaffolds for such complexes, we performed a comprehensive genomic analysis of Nocardia species, revealing the prevalence of siderophore biosynthetic gene clusters, including the highly conserved nocobactin NA-like clusters. From N. coubleae DSM 44960, we isolated three new siderophores, coublibactins A-C (1-3), along with eight congeners (4-11) with known planar structures, all characterized by exceptional iron-binding affinity. Subsequent gallium substitution yielded gallium complexes (Ga-1-11). Among these, Ga-6 exhibited significant Anticancer activity against human acute promyelocytic leukemia NB4 cells with IC50 value of 1.35 μM. Pharmacological studies showed that Ga-6 induces cell cycle arrest and Apoptosis in NB4 cells. Our findings revealed microbial siderophores as promising scaffolds for the design of next-generation metal-based Anticancer therapeutics, particularly gallium-based agents.

Keywords

Anticancer agents; Galium-based complexes; Nocardia; Siderophores.

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