2. Academic Validation
  3. Screening, Discovery, and Optimization of the Natural Antitubercular Chlorflavonin from a Marine-Derived Fungal Library

Screening, Discovery, and Optimization of the Natural Antitubercular Chlorflavonin from a Marine-Derived Fungal Library

  • J Nat Prod. 2025 Feb 28;88(2):522-529. doi: 10.1021/acs.jnatprod.4c01374.
Cui-Fang Wang 1,  Wen-Hui Wang 1,  Ying Xu 1,  Qun Zhang 1,  Mei-Yan Wei 1,  Yu-Cheng Gu 2,  Tong-Yi Xu 3,  Chang-Lun Shao 1
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China.
  • 2 Syngenta Jealott's Hill International Research Centre, Bracknell, Berkshire RG42 6EY, U.K.
  • 3 Department of Cardiovascular and Thoracic Surgery, No. 971 Hospital of PLA Navy, Qingdao 266071, People's Republic of China.
PMID: 39813394 DOI: 10.1021/acs.jnatprod.4c01374
Abstract

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), is still a leading cause of mortality worldwide. Fifty-fungi from a marine-derived Fungal library were screened for anti-Mtb activity, and an Aspergillus candidus strain with strong anti-Mtb activity was found. Three known Flavones, chlorflavonin (1), dechlorflavonin (2), and bromoflavone (3), were isolated from this fungus. Chlorflavonin and bromoflavone showed inhibitory activity with MIC90 values of 2.6 and 1.2 μM, respectively. In combination with molecular docking, a series of new chlorflavonin derivatives (4-41) were rationally designed and semisynthesized. Three new derivatives substituted with (2)-chlorocinnamate (14), (3)-chlorocinnamate (15), and benzoate (18) at position 2' showed MIC90 values ranging from 0.7 to 1.0 μM, having the potential to be further explored as antitubercular agents.

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