Polypropionate Derivatives with Mycobacterium tuberculosis Protein Tyrosine Phosphatase B Inhibitory Activities from the Deep-Sea-Derived Fungus Aspergillus fischeri FS452

• Published in: Journal of natural products (Washington, D.C.) Vol. 82; no. 12; pp. 3440 - 3449
• Main Authors: Liu, Zhaoming, Wang, Qinglin, Li, Saini, Cui, Hui, Sun, Zhanghua, Chen, Dongni, Lu, Yongjun, Liu, Hongxin, Zhang, Weimin
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 27.12.2019; Amer Chemical Soc
• Subjects: Aspergillus fischeri; Chemistry, Medicinal; circular dichroism spectroscopy; enzyme kinetics; fungi; hydrophobicity; inhibitory concentration 50; Life Sciences & Biomedicine; Mycobacterium tuberculosis; Pharmacology & Pharmacy; Plant Sciences; protein-tyrosine-phosphatase; Science & Technology; spectral analysis; structure-activity relationships
• ISSN: 0163-3864; 1520-6025; 1520-6025
• DOI: 10.1021/acs.jnatprod.9b00834

Fiscpropionates A–F (1–6), six new polypropionate derivatives featuring an unusual long hydrophobic chain, were isolated from the deep-sea-derived fungus Aspergillus fischeri FS452. Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configurations were determined by J-HMBC analysis, electronic circular dichroism (ECD) calculations, and the modified Mosher’s method. This is the first discovery of polypropionates from marine-derived fungi, and compounds 4 and 5 represent the first examples of polypropionate derivatives containing a 3-hydroxypiperidin-2-one as part of an imide linkage. In addition, compounds 1–4 exhibited significant inhibitory activities against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with the IC50 values of 5.1, 12, 4.0, and 11 μM, respectively. Enzyme kinetic experiments suggested that they all acted through a noncompetitive mechanism. A preliminary structure–activity relationship is discussed.